Messenger RNA

Messenger RNA, commonly abbreviated as mRNA, is a single-stranded ribonucleic acid molecule that carries genetic information from DNA to the ribosome, where it directs the synthesis of proteins. It plays a central role in the flow of genetic information from DNA to protein, forming a core element of the central dogma of molecular biology. Through transcription, processing, translation, and eventual degradation, mRNA molecules facilitate the expression of genes in all living cells.

Structure and Function

mRNA corresponds to a gene’s nucleotide sequence and contains codons made up of three ribonucleotides. Each codon specifies a particular amino acid, except for stop codons that terminate translation. Together with transfer RNA (tRNA) and ribosomal RNA (rRNA), mRNA enables the assembly of amino acids into polypeptide chains.
tRNA molecules recognise codons and deliver the appropriate amino acids, while rRNA forms the catalytic and structural framework of ribosomes. The precise sequence of nucleotides within mRNA determines the sequence of amino acids, ensuring accurate protein synthesis.
The concept of mRNA was proposed in 1960 by Sydney Brenner and Francis Crick. It was first identified experimentally in 1961 by two independent research groups. As the molecule that conveys genetic information from DNA, it was named messenger RNA by François Jacob and Jacques Monod.

Transcription: The Synthesis of mRNA

Transcription is the process by which RNA polymerase uses a DNA template to generate pre-mRNA (in eukaryotes) or mature mRNA (in prokaryotes). During transcription, RNA polymerase separates the DNA strands and synthesises a complementary RNA molecule.
A notable chemical distinction between RNA and DNA is the substitution of uracil (U) for thymine (T). Uracil pairs with adenine (A) during transcription, allowing the RNA chain to carry genetic information. The evolutionary history of this difference is often linked to the RNA World hypothesis, which proposes that early forms of life relied on RNA before the emergence of DNA-based genomes.
In prokaryotes, mRNA transcripts often require little or no post-transcriptional modification and can be translated while still being synthesised. By contrast, eukaryotic transcripts undergo extensive processing within the nucleus before translation.

Eukaryotic pre-mRNA Processing

Eukaryotic pre-mRNA requires several processing steps to form a mature mRNA molecule capable of being exported to the cytoplasm and translated into protein.
RNA splicingSplicing removes introns, the non-coding regions, and joins together exons, the coding sequences. The spliced exon sequence forms the final coding template used during translation.
5′ cappingShortly after transcription begins, the nascent mRNA receives a 7-methylguanosine cap at its 5′ end. This cap protects the RNA from enzymatic degradation, facilitates ribosomal recognition, and is tightly coupled to ongoing transcription.
RNA editingIn some cases, nucleotides within the mRNA sequence are altered after transcription. Examples include the editing of apolipoprotein B mRNA in humans and adenosine-to-inosine (A-to-I) editing performed by ADAR enzymes. Editing can modify coding sequences or alter structural features of the transcript.
PolyadenylationMost eukaryotic mRNAs receive a polyadenylated tail—typically around 100–250 adenine residues—at their 3′ end. This tail enhances stability, promotes nuclear export, and aids in translation. Polyadenylation occurs when the primary transcript is cleaved at a poly(A) site and a series of adenosine residues is added by polyadenylate polymerase.
Although poly(A) tails in eukaryotes generally stabilise mRNAs, short polyadenylated segments can also occur in prokaryotes, where they facilitate mRNA degradation.

Transport of mRNA

In eukaryotic cells, transcription occurs in the nucleus and translation in the cytoplasm, making mRNA export a critical process. Mature mRNAs are recognised by processing-dependent markers such as the 5′ cap, the poly(A) tail, and specific RNA-binding proteins.
mRNA is exported through nuclear pores via interactions with cap-binding proteins (such as CBP20 and CBP80) and components of the transcription-export (TREX) complex. Multiple export routes exist, and additional pathways operate in specialised cells.
In complex cell types such as neurons, mRNAs can be transported to precise subcellular regions. For example, certain transcripts travel from the cell body to dendrites, where local translation occurs near synapses. mRNAs like those coding for Arc/Arg3.1 or actin localise to synapses in response to stimulation. Transport involves RNA-binding proteins such as ZBP1, motor proteins, and cytoskeletal tracks. Local translation is initiated when regulatory proteins are modified, for instance via phosphorylation.

Translation and Protein Synthesis

Once in the cytoplasm, mature mRNA interacts with ribosomes to guide protein production in a process known as translation. Codons in the mRNA are read sequentially, and tRNA molecules deliver the corresponding amino acids. The ribosome catalyses peptide-bond formation, generating a polypeptide chain that will fold into a functional protein.
Translation continues until a stop codon is encountered. Following translation, mRNAs may be used repeatedly until they are no longer needed and are subsequently degraded.

Degradation and Turnover

The lifespan of an mRNA molecule varies widely, often depending on its sequence features and associated regulatory proteins. Degradation ensures that proteins are produced only when needed and allows rapid adjustment of gene expression. Various pathways degrade mRNA, including exonucleolytic decay and endonuclease-mediated cleavage.
Poly(A) tail shortening typically initiates degradation in eukaryotes, whereas in prokaryotes, polyadenylation can act as a signal that promotes decay.

Significance in Gene Expression

mRNA is fundamental to cellular biology because it bridges genomic information and protein synthesis. The regulation of transcription, processing, export, translation, and degradation collectively determines gene-expression patterns. By controlling the stability and localisation of mRNA, cells adapt their protein production to developmental cues, environmental signals, and metabolic needs.