Messenger RNA

The "life cycle" of an mRNA in a eukaryotic cell. RNA is transcribed in the nucleus; after processing, it is transported to the cytoplasm and translated by the ribosome. Finally, the mRNA is degraded.

Messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.

mRNA is created during the process of transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and the ribosome creates the protein utilizing amino acids carried by transfer RNA (tRNA). This process is known as translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of genetic information in a biological system.

As in DNA, genetic information in mRNA is contained in the sequence of nucleotides, which are arranged into codons consisting of three ribonucleotides each. Each codon codes for a specific amino acid, except the stop codons, which terminate protein synthesis. The translation of codons into amino acids requires two other types of RNA: transfer RNA, which recognizes the codon and provides the corresponding amino acid, and ribosomal RNA (rRNA), the central component of the ribosome's protein-manufacturing machinery.

The concept of mRNA was first conceived by Sydney Brenner and Francis Crick in 1960 during a conversation with François Jacob. In May 1961, messenger RNA was experimentally characterized in two back-to-back Nature papers: one by Brenner, Jacob, and Meselson, and one by Gros and colleagues (including Watson). While analyzing the data in preparation for publication, Jacob and Jacques Monod coined the term "messenger RNA".

Synthesis

RNA polymerase transcribes a DNA strand to form mRNA

The brief existence of an mRNA molecule begins with transcription, and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic mRNA molecules do not. A molecule of eukaryotic mRNA and the proteins surrounding it are together called a messenger RNP.

Transcription

Transcription (genetics)
Transcription is the process by which genetic information stored in DNA is copied into RNA by the enzyme RNA polymerase. During transcription, RNA polymerase binds to a promoter sequence on the DNA and synthesizes a complementary RNA strand (mRNA) from the DNA template.

This process differs between prokaryotes and eukaryotes. In prokaryotes, transcription occurs in the cytoplasm. Because prokaryotes lack a membrane-bound nucleus, ribosomes can attach to the nascent mRNA strand and begin translation while transcription is still in progress.

In eukaryotes, transcription occurs within the cell nucleus. The initial product of transcription is not functional mRNA but is termed precursor mRNA or pre-mRNA. This pre-mRNA must undergo extensive processing (including 5' capping, splicing to remove non-coding introns, and 3' polyadenylation) to become mature mRNA. Once processed, the mature mRNA is exported from the nucleus to the cytoplasm for translation.

Uracil substitution for thymine

Whereas DNA contains thymine (T), RNA contains uracil (U). During the process of transcription, the enzyme RNA polymerase incorporates uracil opposite adenine bases located on the DNA template strand. Therefore, the resulting RNA transcript contains uracil in the positions where the coding DNA strand contains thymine.

Structurally, uracil–adenine (U–A) base pairs closely resemble thymine–adenine (T–A) base pairs, which ensures that the genetic information carried by the sequence is faithfully preserved.

A frequently cited explanation for the presence of thymine in DNA involves the necessity of genome maintenance. Because cytosine can spontaneously deaminate to form uracil, DNA repair systems recognize uracil as a form of damage. The utilization of thymine as a standard base allows the cell to distinguish legitimate bases from errors, thereby maintaining uracil as a specific signal for repair.

Eukaryotic pre-mRNA processing

Post-transcriptional modification

DNA gene is transcribed to pre-mRNA, which is then processed to form a mature mRNA, and then lastly translated by a ribosome to a protein

Processing of mRNA differs greatly among eukaryotes, bacteria, and archaea. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires several processing steps before its transport to the cytoplasm and its translation by the ribosome.

Splicing

RNA splicing
The extensive processing of eukaryotic pre-mRNA that leads to the mature mRNA is the RNA splicing, a mechanism by which introns or outrons (non-coding regions) are removed and exons (coding regions) are joined.

5' cap addition

5' cap

A 5' cap (also termed an RNA cap, an RNA 7-methylguanosine cap, or an RNA m⁷G cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases.

Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction.

Editing

In some instances, an mRNA molecule is edited, which changes the nucleotide composition of the transcript. A prominent example in humans involves the apolipoprotein B mRNA. In certain tissues, RNA editing of this transcript creates a premature stop codon, which results in the production of a shorter protein variant. Another well studied mechanism is A-to-I (adenosine-to-inosine) editing. This reaction is catalyzed by ADAR enzymes (adenosine deaminase acting on RNA) and typically occurs within double-stranded RNA regions. A-to-I editing may occur in both coding sequences and untranslated regions. Through these modifications, the process can affect protein recoding, RNA structure, and gene regulation.

Polyadenylation

Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common. The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.

Polyadenylation occurs during and/or immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 200–250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase. Just as in alternative splicing, there can be more than one polyadenylation variant of an mRNA.

Polyadenylation site mutations can occur. The primary RNA transcript of a gene is cleaved at the poly(A) addition site, and about 150–250 adenosines are added to the 3′ end of the RNA as a poly(A) tail. If this site is altered, cleavage and polyadenylation can shift to a downstream poly(A) site, producing an abnormally long and unstable mRNA.

Transport

Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the nucleus to the cytoplasm—a process that may be regulated by different signaling pathways. Mature mRNAs are recognized by their processed modifications and then exported through the nuclear pore by binding to the cap-binding proteins CBP20 and CBP80, as well as the transcription/export complex (TREX). Multiple mRNA export pathways have been identified in eukaryotes.

In spatially complex cells, some mRNAs are transported to particular subcellular destinations. In mature neurons, certain mRNA are transported from the soma to dendrites. One site of mRNA translation is at polyribosomes selectively localized beneath synapses. The mRNA for Arc/Arg3.1 is induced by synaptic activity and localizes selectively near active synapses based on signals generated by NMDA receptors. Other mRNAs also move into dendrites in response to external stimuli, such as β-actin mRNA. For export from the nucleus, actin mRNA associates with ZBP1 and later with 40S subunit. The complex is bound by a motor protein and is transported to the target location (neurite extension) along the cytoskeleton. Eventually ZBP1 is phosphorylated by Src in order for translation to be initiated. In developing neurons, mRNAs are also transported into growing axons and especially growth cones. Many mRNAs are marked with so-called "zip codes", which target their transport to a specific location. mRNAs can also transfer between mammalian cells through structures called tunneling nanotubes.

Translation

Translation (biology)

Because prokaryotic mRNA does not need to be processed or transported, translation by the ribosome can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is coupled to transcription and occurs co-transcriptionally.

In eukaryotic cells the process of translation starts with the information stored in the nucleotide sequence of DNA. This is first transformed into mRNA, then transfer RNA (tRNA) specifies which three-nucleotide codon from the genetic code corresponds to which amino acid.

Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by ribosomes. Translation may occur at ribosomes free in the cytoplasm, or targeted to the endoplasmic reticulum by the signal recognition particle. Therefore, unlike in prokaryotes, eukaryotic translation is not directly coupled to transcription. In some contexts, protein abundance can increase even when mRNA abundance decreases, because translation efficiency and protein turnover are regulated independently of transcript levels; this has been reported for mRNA and protein levels of EEF1A1 in breast cancer.

Structure

Coding regions

Coding region
Coding regions are composed of codons, which are decoded and translated into proteins by the ribosome; in eukaryotes usually into one and in prokaryotes usually into several. Coding regions begin with the start codon and end with a stop codon. In general, the start codon is an AUG triplet and the stop codon is UAG ("amber"), UAA ("ochre"), or UGA ("opal"). The coding regions tend to be stabilized by internal base pairs; this impedes degradation. In addition to being protein-coding, portions of coding regions may serve as regulatory sequences in the pre-mRNA as exonic splicing enhancers or exonic splicing silencers.

Untranslated regions

5' UTR

Universal structure of eukaryotic mRNA, showing the structure of the 5' and 3' UTRs.

Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region (5' UTR) and three prime untranslated region (3' UTR), respectively. These regions are transcribed with the coding region and thus are exonic as they are present in the mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency. The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs. Genetic variants in 3' UTR have also been implicated in disease susceptibility because of the change in RNA structure and protein translation.

The stability of mRNAs may be controlled by the 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called ribonucleases and for ancillary proteins that can promote or inhibit RNA degradation. (See also, C-rich stability element.)

Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing the ribosome's ability to bind to the mRNA. MicroRNAs bound to the 3' UTR also may affect translational efficiency or mRNA stability.

Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can also be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation.

Some of the elements contained in untranslated regions form a characteristic secondary structure when transcribed into RNA. These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins to bind. One class of mRNA element, the riboswitches, directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases, the mRNA regulates itself.

Poly(A) tail

Polyadenylation
The 3' poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the 3' end of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation.

Monocistronic versus polycistronic mRNA

Cistron
An mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein chain (polypeptide). This is the case for most of the eukaryotic mRNAs. On the other hand, polycistronic mRNA carries several open reading frames (ORFs), each of which is translated into a polypeptide. These polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequence is grouped and regulated together in a regulatory region, containing a promoter and an operator. Most of the mRNA found in bacteria and archaea is polycistronic, as is the human mitochondrial genome. Dicistronic or bicistronic mRNA encodes only two proteins.

mRNA circularization

In eukaryotes mRNA molecules form circular structures due to an interaction between the eIF4E and poly(A)-binding protein, which both bind to eIF4G, forming an mRNA-protein-mRNA bridge. Circularization is thought to promote cycling of ribosomes on the mRNA leading to time-efficient translation, and may also function to ensure only intact mRNA are translated (partially degraded mRNA characteristically have no m7G cap, or no poly-A tail).

Other mechanisms for circularization exist, particularly in viruses. In several RNA viruses, long-distance RNA interactions and/or protein-mediated bridges between the 5' and 3' ends can promote translation and genome replication.

RNA virus genomes (the + strands of which are translated as mRNA) are also commonly circularized.

Degradation

Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour. However, the lifetime averages between 1 and 3 minutes, making bacterial mRNA much less stable than eukaryotic mRNA. In mammalian cells, mRNA lifetimes range from several minutes to days. The greater the stability of an mRNA the more protein may be produced from that mRNA. The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs. There are many mechanisms that lead to the destruction of an mRNA, some of which are described below.

Prokaryotic mRNA degradation

Overview of mRNA decay pathways in the different life domains.

In general, in prokaryotes the lifetime of mRNA is much shorter than in eukaryotes. Prokaryotes degrade messages by using a combination of ribonucleases, including endonucleases, 3' exonucleases, and 5' exonucleases. In some instances, small RNA molecules (sRNA) tens to hundreds of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage by RNase III. It was recently shown that bacteria also have a sort of 5' cap consisting of a triphosphate on the 5' end. Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the exonuclease RNase J, which degrades 5' to 3'.

Eukaryotic mRNA turnover

Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay. Messages that are being actively translated are typically associated with cap-binding and translation initiation factors and with poly(A)-binding protein, which can antagonize deadenylation and decapping and help protect mRNA ends from decay machinery. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as P-bodies. The poly(A) tail of the mRNA is shortened by specialized exonucleases that are targeted to specific messenger RNAs by a combination of cis-regulatory sequences on the RNA and trans-acting RNA-binding proteins. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the cap binding complex. The message is then subject to degradation by either the exosome complex or the decapping complex. In this way, translationally inactive messages can be destroyed quickly, while active messages remain intact. The mechanism by which translation stops and the message is handed-off to decay complexes is not understood in detail. The majority of mRNA decay was believed to be cytoplasmic; however, recently, a novel mRNA decay pathway was described, which starts in the nucleus.

AU-rich element decay

The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal. Loss of the poly(A) tail is thought to promote mRNA degradation by facilitating attack by both the exosome complex and the decapping complex. Rapid mRNA degradation via AU-rich elements is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF). AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like c-Jun and c-Fos.

Nonsense-mediated decay

Nonsense-mediated decay
Eukaryotic messages are subject to surveillance by nonsense-mediated decay (NMD), which checks for the presence of premature stop codons (nonsense codons) in the message. These can arise via incomplete splicing, V(D)J recombination in the adaptive immune system, mutations in DNA, transcription errors, leaky scanning by the ribosome causing a frame shift, and other causes. Detection of a premature stop codon triggers mRNA degradation by 5' decapping, 3' poly(A) tail removal, or endonucleolytic cleavage.

Small interfering RNA (siRNA)

siRNA
In metazoans, small interfering RNAs (siRNAs) processed by Dicer are incorporated into a complex known as the RNA-induced silencing complex or RISC. This complex contains an endonuclease that cleaves perfectly complementary messages to which the siRNA binds. The resulting mRNA fragments are then destroyed by exonucleases. siRNA is commonly used in laboratories to block the function of genes in cell culture. It is thought to be part of the innate immune system as a defense against double-stranded RNA viruses.

MicroRNA (miRNA)

microRNA
MicroRNAs (miRNAs) are small RNAs that typically are partially complementary to sequences in metazoan messenger RNAs. Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation. The mechanism of action of miRNAs is the subject of active research.

Other decay mechanisms

There are other ways by which messages can be degraded, including non-stop decay and silencing by Piwi-interacting RNA (piRNA), among others.

Applications

mRNA vaccine
The administration of a nucleoside-modified messenger RNA sequence can cause a cell to make a protein, which in turn could directly treat a disease or could function as a vaccine; more indirectly the protein could drive an endogenous stem cell to differentiate in a desired way.

The primary challenges of RNA therapy center on delivering the RNA to the appropriate cells. Challenges include the fact that naked RNA sequences naturally degrade after preparation; they may trigger the body's immune system to attack them as an invader; and they are impermeable to the cell membrane. Once within the cell, they must then leave the cell's transport mechanism to take action within the cytoplasm, which houses the necessary ribosomes.

Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 "after the development of a broadly applicable in vitro transfection technique." In the 1990s, mRNA vaccines for personalized cancer were developed, typically using unmodified mRNA. mRNA based therapies continue to be investigated as a method of treatment or therapy for both cancer as well as auto-immune, metabolic, and respiratory inflammatory diseases. Gene editing therapies such as CRISPR may also benefit from using mRNA to induce cells to make the desired Cas protein.

Since the 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs". The first mRNA-based vaccines received restricted authorization and were rolled out across the world during the COVID-19 pandemic by Pfizer–BioNTech COVID-19 vaccine and Moderna, for example.

The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for the development of effective mRNA vaccines against COVID-19. New approaches to modulate RNA levels as a therapeutics include the use of antisense oligonucleotides, including for neurodevelopment diseases associated with high mortality.

History

Several molecular biology studies during the early 1950s suggested that RNA played a role in protein synthesis, though the specific role remained unclear. For example, in one of the earliest reports, Jacques Monod and his team showed that RNA synthesis was necessary for protein synthesis, specifically during the production of the enzyme β-galactosidase in the bacterium E. coli. Arthur Pardee also found similar RNA accumulation in 1954. In 1953, Alfred Hershey, June Dixon, and Martha Chase studied E. coli infected with bacteriophage T2 and reported that the bacterium's own DNA decreased while the phage's DNA built up inside the infected cells (including DNA containing 5-hydroxymethylcytosine). In hindsight, this has been discussed as part of the chain of observations that led to the concept of mRNA, and it was not recognized at the time as such.

The idea of mRNA was first conceived by Sydney Brenner and Francis Crick on 15 April 1960 at King's College, Cambridge, while François Jacob was telling them about a recent experiment conducted by Arthur Pardee, himself, and Monod (the so-called PaJaMo experiment, which did not prove mRNA existed but suggested the possibility of its existence). With Crick's encouragement, Brenner and Jacob immediately set out to test this new hypothesis, and they contacted Matthew Meselson at the California Institute of Technology for assistance. During the summer of 1960, Brenner, Jacob, and Meselson conducted an experiment in Meselson's laboratory at Caltech which was the first to prove the existence of mRNA. That fall, Jacob and Monod coined the name "messenger RNA" and developed the first theoretical framework to explain its function.

In February 1961, James Watson revealed that his Harvard-based research group had been right behind them with a series of experiments whose results pointed in roughly the same direction. Brenner and the others agreed to Watson's request to delay publication of their research findings. As a result, the Brenner and Watson articles were published simultaneously in the same issue of Nature in May 1961, while that same month, Jacob and Monod published their theoretical framework for mRNA in the Journal of Molecular Biology.

References

Alberts, Bruce, Johnson, Alexander, Lewis, Julian, Raff, Martin, Roberts, Keith, Walter, Peter, Molecular Biology of the Cell, 4th, Garland Science, New York, 2002, From RNA to Protein, 2026-02-04
Messenger RNA (mRNA), National Human Genome Research Institute, 2026-02-04
Crick, F, Central dogma of molecular biology, Nature, 1970, 227, 5258, 561–563, 10.1038/227561a0, 4913914
Brenner S, Jacob F, Meselson M, An Unstable Intermediate Carrying Information from Genes to Ribosomes for Protein Synthesis, Nature, 1961, 190, 4776, 576–581, 10.1038/190576a0, 20446365
Gros F, Hiatt H, Gilbert W, Kurland CG, Risebrough RW, Watson JD, Unstable Ribonucleic Acid Revealed by Pulse Labelling of , Escherichia coli, Nature, 1961, 190, 4776, 581–585, 10.1038/190581a0, 13708983
Who named messenger RNA?, François Jacob, Cold Spring Harbor Laboratory DNA Learning Center, Cold Spring Harbor Laboratory, 2026-02-04
Mitchell SF, Parker R, Principles and properties of eukaryotic mRNPs, Molecular Cell, 2014-05-22, 54, 4, 547–558, 10.1016/j.molcel.2014.04.033, 24856220
Alberts, Bruce, Johnson, Alexander, Lewis, Julian, Raff, Martin, Roberts, Keith, Walter, Peter, Molecular Biology of the Cell, 4th, Garland Science, New York, 2002, From DNA to RNA, 2025-12-17
Cooper, Geoffrey M., The Cell: A Molecular Approach, 2nd, Sinauer Associates, Sunderland, MA, 2000, Transcription in Prokaryotes, 2025-12-17
Irastortza-Olaziregi, Mikel, Amster-Choder, Orna, Coupled Transcription-Translation in Prokaryotes: An Old Couple With New Surprises, Frontiers in Microbiology, 2021, 11, 624830, 10.3389/fmicb.2020.624830, 33552035, 7858274, free
Hocine, Sami, Singer, Robert H., Grünwald, David, RNA processing and export, Cold Spring Harbor Perspectives in Biology, December 2010, 2, 12, a000752, 10.1101/cshperspect.a000752, 20961978, 2982171, free
Cooper, Geoffrey M., The Cell: A Molecular Approach, 2nd, Sinauer Associates, Sunderland, MA, 2000, RNA Processing and Turnover, 2025-12-17
Cooper, Geoffrey M., The Cell: A Molecular Approach, 2nd, Sinauer Associates, Sunderland, MA, 2000, The Molecular Composition of Cells, 2025-12-17
Vértessy BG, Tóth J, Keeping Uracil Out of DNA: Physiological Role, Structure and Catalytic Mechanism of dUTPases, Acc. Chem. Res., 2009, 42, 1, 97–106, 10.1021/ar800114w, 18837522, 2732909, free
Watson JD, James Watson, Molecular Biology of the Gene, 7th edition, Pearson Higher Ed USA, February 22, 2013
10.1038/s41580-022-00545-z, The physiology of alternative splicing, 2023, Nature Reviews Molecular Cell Biology, 24, 4, 242–254, 36229538, Marasco LE, Kornblihtt AR, subscription
10.1038/s41576-022-00556-8, Regulation of pre-mRNA splicing: Roles in physiology and disease, and therapeutic prospects, 2023, Nature Reviews Genetics, 24, 4, 251–269, 36526860, Rogalska ME, Vivori C, Valcárcel J, subscription
Ramanathan, Anand, Robb, G. Brett, Chan, Siu-Hong, mRNA capping: biological functions and applications, Nucleic Acids Research, 2016-09-19, 44, 16, 7511–7526, 10.1093/nar/gkw551, 27317694, 5027499
Hsin, Jing-Ping, Manley, James L, The RNA polymerase II CTD coordinates transcription and RNA processing, Genes & Development, 2012-10-01, 26, 19, 2119–2137, 10.1101/gad.200303.112, 23028141, 3465734
10.1186/gm508, free, Adenosine-to-inosine RNA editing and human disease, 2013, Genome Medicine, 5, 11, 24289319, 3979043, Slotkin W, Nishikura K
Choi YS, Patena W, Leavitt AD, McManus MT, Widespread RNA 3'-end oligouridylation in mammals, RNA, 18, 3, 394–401, March 2012, 22291204, 3285928, 10.1261/rna.029306.111
Hajnsdorf E,Kaberdin VR, RNA polyadenylation and its consequences in prokaryotes, Philosophical Transactions of the Royal Society B: Biological Sciences, 2018, 373, 1762, 10.1098/rstb.2018.0166, 6232592, 30397102
Curinha, Ana, Oliveira Braz, Sandra, Pereira-Castro, Isabel, Cruz, Andrea, Moreira, Alexandra, Implications of polyadenylation in health and disease, Nucleus, 2014-10-31, 5, 6, 508–519, 10.4161/nucl.36360, 25484187, 4615197
Di Giammartino, Dafne Campigli, Nishida, Kensei, Manley, James L., Mechanisms and consequences of alternative polyadenylation, Molecular Cell, 2011-09-16, 43, 6, 853–866, 10.1016/j.molcel.2011.08.017, 21925375, 3194005
Quaresma AJ, Sievert R, Nickerson JA, Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway, Molecular Biology of the Cell, 24, 8, 1208–1221, April 2013, 23427269, 3623641, 10.1091/mbc.E12-06-0450
Kierzkowski D, Kmieciak M, Piontek P, Wojtaszek P, Szweykowska-Kulinska Z, Jarmolowski A, The Arabidopsis CBP20 targets the cap-binding complex to the nucleus, and is stabilized by CBP80, The Plant Journal, 59, 5, 814–825, September 2009, 19453442, 10.1111/j.1365-313X.2009.03915.x, free
Strässer K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondón AG, Aguilera A, Struhl K, Reed R, Hurt E, TREX is a conserved complex coupling transcription with messenger RNA export, Nature, 417, 6886, 304–308, May 2002, 11979277, 10.1038/nature746, 2002Natur.417..304S, 1112194
Katahira J, Yoneda Y, Roles of the TREX complex in nuclear export of mRNA, RNA Biology, 6, 2, 149–152, 27 October 2014, 19229134, 10.4161/rna.6.2.8046, free
Cenik C, Chua HN, Zhang H, Tarnawsky SP, Akef A, Derti A, Tasan M, Moore MJ, Palazzo AF, Roth FP, Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes, PLOS Genetics, 7, 4, e1001366, April 2011, 21533221, 3077370, 10.1371/journal.pgen.1001366, free
Steward O, Levy WB, Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus, The Journal of Neuroscience, 2, 3, 284–291, March 1982, 7062109, 6564334, 10.1523/JNEUROSCI.02-03-00284.1982
Steward O, Worley PF, Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation, Neuron, 30, 1, 227–240, April 2001, 11343657, 10.1016/s0896-6273(01)00275-6, 13395819, free
Job C, Eberwine J, Localization and translation of mRNA in dendrites and axons, Nature Reviews. Neuroscience, 2, 12, 889–898, December 2001, 11733796, 10.1038/35104069, James Eberwine, 5275219
Oleynikov Y, Singer RH, Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization, Current Biology, 13, 3, 199–207, February 2003, 12573215, 4765734, 10.1016/s0960-9822(03)00044-7, 2003CBio...13..199O
Hüttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X, Bassell GJ, Condeelis J, Singer RH, 6, Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1, Nature, 438, 7067, 512–515, November 2005, 16306994, 10.1038/nature04115, 2453397, 2005Natur.438..512H
Oleynikov Y, Singer RH, RNA localization: different zipcodes, same postman?, Trends in Cell Biology, 8, 10, 381–383, October 1998, 9789325, 2136761, 10.1016/s0962-8924(98)01348-8
Ainger K, Avossa D, Diana AS, Barry C, Barbarese E, Carson JH, Transport and localization elements in myelin basic protein mRNA, The Journal of Cell Biology, 138, 5, 1077–1087, September 1997, 9281585, 2136761, 10.1083/jcb.138.5.1077
Haimovich G, Ecker CM, Dunagin MC, Eggan E, Raj A, Gerst JE, Singer RH, Intercellular mRNA trafficking via membrane nanotube-like extensions in mammalian cells, Proceedings of the National Academy of Sciences of the United States of America, 114, 46, E9873–E9882, November 2017, 29078295, 5699038, 10.1073/pnas.1706365114, 2017PNAS..114E9873H, free
Haimovich G, Dasgupta S, Gerst JE, RNA transfer through tunneling nanotubes, Biochemical Society Transactions, February 2021, 49, 1, 145–160, 10.1042/BST20200113, 33367488, 229689880, subscription
10.3389/fmicb.2020.624830, free, Coupled Transcription-Translation in Prokaryotes: An Old Couple with New Surprises, 2021, Frontiers in Microbiology, 11, Irastortza-Olaziregi M, Amster-Choder O, 624830, 33552035, 7858274
Crick FH, The origin of the genetic code, Journal of Molecular Biology, 38, 3, 367–379, December 1968, 4887876, 10.1016/0022-2836(68)90392-6, 4144681
Lin CY, Beattie A, Baradaran B, Dray E, Duijf PH, Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress, Scientific Reports, 8, 1, 13904, September 2018, 30224719, 6141510, 10.1038/s41598-018-32272-x, 2018NatSR...813904L
Vogel C, Marcotte EM, Insights into the regulation of protein abundance from proteomic and transcriptomic analyses, Nature Reviews Genetics, 13, 4, 227–232, March 2012, 22411467, 3654667, 10.1038/nrg3185
Shabalina SA, Ogurtsov AY, Spiridonov NA, A periodic pattern of mRNA secondary structure created by the genetic code, Nucleic Acids Research, 34, 8, 2428–2437, 2006, 16682450, 1458515, 10.1093/nar/gkl287
Katz L, Burge CB, Widespread selection for local RNA secondary structure in coding regions of bacterial genes, Genome Research, 13, 9, 2042–2051, September 2003, 12952875, 403678, 10.1101/gr.1257503
Mignone F, Gissi C, Liuni S, Pesole G, Untranslated regions of mRNAs, Genome Biology, 2002, 3, 3, reviews0004.1–reviews0004.10, 10.1186/gb-2002-3-3-reviews0004, 11897027, 139399, free
Lu YF, Mauger DM, Goldstein DB, Urban TJ, Weeks KM, Bradrick SS, IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance, Scientific Reports, 5, 16037, November 2015, 26531896, 4631997, 10.1038/srep16037, 2015NatSR...516037L
Brennecke J, Stark A, Russell RB, Cohen SM, Principles of microRNA-target recognition, PLOS Biology, 3, 3, March 2005, 15723116, 1043860, 10.1371/journal.pbio.0030085, free
Liu, Zesheng, Reches, Myriam, Groisman, Irina, Engelberg-Kulka, Hanna, The nature of the minimal 'selenocysteine insertion sequence' (SECIS) in , Escherichia coli, Nucleic Acids Research, 1998, 26, 4, 896–902, 10.1093/nar/26.4.896, 147357
Serganov, Alexander, Nudler, Evgeny, A Decade of Riboswitches, Cell, 2013, 152, 1–2, 17–24, 10.1016/j.cell.2012.12.024, 4215550
Kozak M, Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles, Microbiological Reviews, 47, 1, 1–45, March 1983, 6343825, 281560, 10.1128/MMBR.47.1.1-45.1983
Niehrs C, Pollet N, Synexpression groups in eukaryotes, Nature, 402, 6761, 483–487, December 1999, 10591207, 10.1038/990025, 1999Natur.402..483N, 4349134
Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, Filipovska A, Mattick JS, John Stamatoyannopoulos, The human mitochondrial transcriptome, Cell, 146, 4, 645–658, August 2011, 21854988, 3160626, 10.1016/j.cell.2011.06.051
Wells SE, Hillner PE, Vale RD, Sachs AB, Circularization of mRNA by eukaryotic translation initiation factors, Molecular Cell, 2, 1, 135–140, July 1998, 9702200, 10.1016/S1097-2765(00)80122-7, 10.1.1.320.5704
López-Lastra M, Rivas A, Barría MI, Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation, Biological Research, 38, 2–3, 121–146, 2005, 16238092, 10.4067/S0716-97602005000200003, free, 10533/176032, free
López-Lastra M, Rivas A, Barría MI, Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation, Biological Research, 38, 2–3, 121–146, 2005, 16238092, 10.4067/S0716-97602005000200003, free, 10533/176032, free
Zhang X, Liang Z, Wang C, Shen Z, Sun S, Gong C, Hu X, Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction, Frontiers in Immunology, 13, 939768, 2022, 35784275, 9247149, 10.3389/fimmu.2022.939768, free
Lewin's genes X, 2011, Jones and Bartlett, Lewin B, Krebs JE, Kilpatrick ST, Goldstein ES, Benjamin Lewin, 10th, Sudbury, Mass., 456641931, registration
Yu J, Russell JE, Structural and functional analysis of an mRNP complex that mediates the high stability of human beta-globin mRNA, Molecular and Cellular Biology, 21, 17, 5879–5888, September 2001, 11486027, 87307, 10.1128/mcb.21.17.5879-5888.2001
Deana A, Celesnik H, Belasco JG, The bacterial enzyme RppH triggers messenger RNA degradation by 5' pyrophosphate removal, Nature, 451, 7176, 355–358, January 2008, 18202662, 10.1038/nature06475, 2008Natur.451..355D, 4321451
Parker R, Sheth U, P bodies and the control of mRNA translation and degradation, Molecular Cell, 25, 5, 635–646, March 2007, 17349952, 10.1016/j.molcel.2007.02.011, free
Chattopadhyay S, Garcia Martinez J, Haimovich G, Fischer J, Khwaja A, Barkai O, Chuartzman SG, Schuldiner M, Elran R, Rosenberg M, Urim S, Deshmukh S, Bohnsack K, Bohnsack M, Perez Ortin J, Choder M, RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway, Nature Communications, 13, November 2022, 1, 7184, 36418294, 10.1038/s41467-022-34417-z, free, 9684461, 2022NatCo..13.7184C
Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M, AU binding proteins recruit the exosome to degrade ARE-containing mRNAs, Cell, 107, 4, 451–464, November 2001, 11719186, 10.1016/S0092-8674(01)00578-5, 14817671, free
Fenger-Grøn M, Fillman C, Norrild B, Lykke-Andersen J, Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping, Molecular Cell, 20, 6, 905–915, December 2005, 16364915, 10.1016/j.molcel.2005.10.031, free
Shaw G, Kamen R, A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation, Cell, 46, 5, 659–667, August 1986, 3488815, 10.1016/0092-8674(86)90341-7, 40332253
Chen CY, Shyu AB, AU-rich elements: characterization and importance in mRNA degradation, Trends in Biochemical Sciences, 20, 11, 465–470, November 1995, 8578590, 10.1016/S0968-0004(00)89102-1
Isken O, Maquat LE, Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function, Genes & Development, 21, 15, 1833–1856, August 2007, 17671086, 10.1101/gad.1566807, free
Obbard DJ, Gordon KH, Buck AH, Jiggins FM, The evolution of RNAi as a defence against viruses and transposable elements, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 364, 1513, 99–115, January 2009, 18926973, 2592633, 10.1098/rstb.2008.0168
Brennecke J, Stark A, Russell RB, Cohen SM, Principles of microRNA-target recognition, PLOS Biology, 3, 3, March 2005, 15723116, 1043860, 10.1371/journal.pbio.0030085, free
Eulalio A, Huntzinger E, Nishihara T, Rehwinkel J, Fauser M, Izaurralde E, Deadenylation is a widespread effect of miRNA regulation, RNA, 15, 1, 21–32, January 2009, 19029310, 2612776, 10.1261/rna.1399509
Siomi MC, Sato K, Pezic D, Aravin AA, PIWI-interacting small RNAs: the vanguard of genome defence, Nature Reviews Molecular Cell Biology, 2011, 12, 4, 246–258
Hajj KA, Whitehead KA, Tools for translation: non-viral materials for therapeutic mRNA delivery, Nature Reviews Materials, 12 September 2017, 2, 10, 17056, 10.1038/natrevmats.2017.56, 2017NatRM...217056H, free
Gousseinov E, Kozlov M, Scanlan C, RNA-Based Therapeutics and Vaccines, Genetic Engineering News, September 15, 2015
Kaczmarek JC, Kowalski PS, Anderson DG, June 2017, Advances in the delivery of RNA therapeutics: from concept to clinical reality, Genome Medicine, 9, 1, 60, 10.1186/s13073-017-0450-0, 5485616, 28655327, free
Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ, Developing mRNA-vaccine technologies, RNA Biology, 9, 11, 1319–30, November 2012, 23064118, 3597572, 10.4161/rna.22269
Pardi N, Hogan MJ, Porter FW, Weissman D, mRNA vaccines: a new era in vaccinology, Nature Reviews Drug Discovery, 2018, 17, 4, 261–279, 10.1038/nrd.2017.243
Sahin, U, Karikó, K, Türeci, Ö, mRNA-based therapeutics: developing a new class of drugs, Nature Reviews Drug Discovery, 2014, 13, 10, 759–780, 10.1038/nrd4278, 25233993
Barbier AJ, Jiang AY, Zhang P, Wooster R, Anderson DG, The clinical progress of mRNA vaccines and immunotherapies, Nature Biotechnology, 40, 6, 840–854, June 2022, 35534554, 10.1038/s41587-022-01294-2, 248667843, free
The Nobel Prize in Physiology or Medicine 2023, 2023-10-03, NobelPrize.org, en-US
2023-10-02, Hungarian and US scientists win Nobel for COVID-19 vaccine discoveries, en, Reuters, 2023-10-03
The Nobel Prize in Physiology or Medicine 2023, 2023-10-03, NobelPrize.org, en-US
Golinski, SR, Soriano, K, Briegel, AC, Burke, MC, Yu, TW, Nakayama, T, Hu, R, Smith, RS, Gene therapy for targeting a prenatally enriched potassium channel associated with severe childhood epilepsy and premature death, 24 October 2024, 10.1101/2024.10.24.620125
Monod J, Pappenheimer AM, Cohen-Bazire G, 1952, La cinétique de la biosynthèse de la β-galactosidase chez E. coli considérée comme fonction de la croissance, Biochimica et Biophysica Acta, fr, 9, 6, 648–660, 10.1016/0006-3002(52)90227-8, 13032175
Pardee AB, Nucleic Acid Precursors and Protein Synthesis, Proceedings of the National Academy of Sciences of the United States of America, 40, 5, 263–270, May 1954, 16589470, 534118, 10.1073/pnas.40.5.263, 1954PNAS...40..263P, free
Hershey AD, Dixon J, Chase M, Nucleic acid economy in bacteria infected with bacteriophage T2. I. Purine and pyrimidine composition, The Journal of General Physiology, 36, 6, 777–789, July 1953, 13069681, 2147416, 10.1085/jgp.36.6.777
Matthew Cobb, Cobb M, 29 June 2015, Who discovered messenger RNA?, Current Biology, 25, 13, R526–R532, 10.1016/j.cub.2015.05.032, 26126273, free, 2015CBio...25.R526C

External links

RNAi Atlas: a database of RNAi libraries and their target analysis results
miRSearch Archived 2012-12-04, at web.archive.org: Tool for finding microRNAs that target mRNA
How mRNA is coded?: YouTube video
What is mRNA?: theconversation.com

Category:RNA
Category:Gene expression
Category:Protein biosynthesis
Category:Molecular genetics
Category:Spliceosome
Category:RNA splicing
Category:Life sciences industry
Category:Molecular biology

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