Messenger RNA (mRNA) is a type of ribonucleic acid that serves as a template for making proteins. In a cell, it is produced from DNA through transcription and conveys the information encoded in a protein-coding gene to a ribosome. The ribosome reads its sequence during translation, assembling amino acids into a protein chain. Unlike DNA, which generally provides long-term genetic storage, mRNA is a working copy whose production, use, and degradation can be regulated. (genome.gov)
Molecular structure
An mRNA molecule consists of a chain of nucleotides containing ribose sugars, phosphate groups, and four principal bases: adenine, guanine, cytosine, and uracil. RNA therefore differs chemically from DNA, which contains deoxyribose and normally uses thymine instead of uracil. Although mRNA is usually single-stranded, it can fold into local structures through pairing between complementary regions. (genome.gov)
The protein-coding region is read as successive three-nucleotide units called codons. Under the genetic code, most codons specify an amino acid, while stop codons signal the end of protein synthesis. Sequences outside the main coding region, called untranslated regions or UTRs, help control translation and RNA stability rather than directly specifying the main protein sequence. (ncbi.nlm.nih.gov)
Most mature, nuclear-encoded mRNAs in eukaryotes carry a modified guanine-containing 5′ cap and a poly(A) tail at their 3′ end. These features influence translation, stability, and transport. The tail is added during RNA processing rather than copied directly from a corresponding stretch of DNA. Some mRNAs, including replication-dependent histone mRNAs in animals, lack the usual poly(A) tail. (ncbi.nlm.nih.gov)
Transcription and maturation
Transcription produces an RNA sequence complementary to one strand of DNA. In eukaryotes, a newly synthesized precursor, or pre-mRNA, usually undergoes several processing steps before functioning as a mature message. These include capping, cleavage of the 3′ end, polyadenylation, and removal of intervening sequences. Processing occurs during or after transcription in the cell nucleus. (genome.gov)
During RNA splicing, introns are removed and retained segments, called exons, are joined. For most nuclear pre-mRNAs, this reaction is performed by a spliceosome, a complex of small RNAs and proteins. Alternative splicing allows different combinations of exons to be incorporated into mature transcripts, so a single gene can produce multiple mRNA forms and potentially different proteins. (ncbi.nlm.nih.gov)
Processed mRNA is exported from the nucleus to the cytoplasm, where translation occurs. This separation distinguishes nuclear gene expression in eukaryotes from that in bacteria, which lack a membrane-bound nucleus. In bacteria, ribosomes can begin translating a message while it is still being transcribed. Bacterial mRNAs also commonly contain several independently translated coding regions, whereas most eukaryotic mRNAs have one principal protein-coding region. (ncbi.nlm.nih.gov)
Role in protein synthesis
Translation involves initiation, elongation, and termination. In the common cap-dependent pathway in eukaryotes, initiation factors recognize the mRNA and recruit a small ribosomal subunit. It scans for a suitable start codon, usually AUG, after which the large subunit joins to form the translating ribosome. The surrounding sequence influences which start site is selected. (ncbi.nlm.nih.gov)
During elongation, transfer RNA molecules pair with successive codons and deliver the corresponding amino acids. The ribosome links these amino acids into a growing chain as it advances along the message in the 5′-to-3′ direction. At a stop codon, release factors promote release of the completed chain. Several ribosomes can translate the same mRNA simultaneously, forming a polysome; a message is therefore not necessarily consumed after producing one protein. (ncbi.nlm.nih.gov)
Regulation and turnover
An mRNA’s abundance is determined by both its rate of production and its rate of degradation. Its contribution to protein output also depends on how efficiently ribosomes translate it. Consequently, equal amounts of two different mRNAs need not produce equal amounts of protein. RNA-binding proteins and regulatory sequences can alter translation, localization, and stability, providing control after transcription has occurred. (ncbi.nlm.nih.gov)
A common eukaryotic decay pathway begins with shortening of the poly(A) tail, followed by removal of the cap and enzymatic breakdown of the RNA. The rates of these processes differ among messages. Other pathways monitor translation and remove defective transcripts, including some containing premature stop codons. Such quality-control mechanisms limit the production of incomplete or abnormal proteins. (ncbi.nlm.nih.gov)
Discovery and engineered applications
Experimental evidence for messenger RNA emerged in 1961. Sydney Brenner, François Jacob, and Matthew Meselson studied bacteriophage-infected bacteria and showed that newly synthesized RNA associated with pre-existing ribosomes. Their work supported the existence of a temporary informational intermediate, rather than a requirement for a separate, newly made ribosome for each protein. Their landmark paper appeared in Nature on May 13, 1961. (nature.com)
Engineered mRNA can be produced outside cells and delivered to them to direct protein production. In mRNA vaccines, the encoded protein acts as an antigen that the immune system can recognize. Lipid nanoparticles provide a delivery system for the RNA. Research on modified nucleosides and delivery methods helped enable mRNA vaccines against COVID-19. The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for discoveries concerning nucleoside base modifications that enabled effective mRNA vaccines against the disease. (nobelprize.org)