What is mRNA? Structure, function and how it differs from tRNA

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Every protein your cells make starts as a message. The gene sits in DNA, safely inside the nucleus, and the cell does not send the original out to the protein-building machinery. It sends a disposable copy instead. That copy is messenger RNA, or mRNA.

The idea of a short-lived messenger was put forward by François Jacob and Jacques Monod, and experiments published in 1961 showed it was real. The same year, Marshall Nirenberg and Heinrich Matthaei fed a synthetic RNA made only of uracil into a cell-free system and got a protein made only of phenylalanine, the first word of the genetic code to be read. Sixty years later, the same molecule became the basis of a new class of vaccines.

Below: a walk along one mRNA from end to end, a comparison with the other two big kinds of RNA, and a message's life from birth to breakdown.

What mRNA does, in one paragraph

mRNA carries the instructions for one protein (or, in bacteria, sometimes several) from a gene to a ribosome. The ribosome reads the message three letters at a time. Each three-letter codon specifies one amino acid, and the ribosome links them in order into a chain that folds into a working protein. When enough copies of the protein have been made, the cell destroys the message. That is not a flaw. Short-lived messages let a cell change what it produces within hours, which is how it responds to food, stress, hormones or infection.

A tour of an mRNA, from the 5' end to the 3' end

RNA strands have direction. Chemists number the carbons in each sugar, and the two ends of a strand are called 5' ("five prime") and 3'. Ribosomes read mRNA from 5' to 3', so that is the order of the tour. What follows describes a typical mature mRNA in a human cell.

1. The 5' cap

The very front of the molecule carries a modified guanine nucleotide, 7-methylguanosine, attached backwards through an unusual 5' to 5' triphosphate bridge. This cap does three jobs. It protects the end from enzymes that chew RNA from the 5' side. It helps the finished message leave the nucleus. And it is the handle that the translation machinery grabs first: a cap-binding protein called eIF4E recognizes it and helps recruit the small ribosomal subunit.

2. The 5' untranslated region (5' UTR)

Between the cap and the first codon lies a stretch that is copied from the gene but never turned into protein. The small ribosomal subunit lands near the cap and scans along this region looking for a start signal. Its length and folding affect how efficiently the message is used: a tightly folded 5' UTR slows scanning, and short "decoy" reading frames inside it can divert ribosomes. Cells use these features to adjust translation quickly without touching the gene.

3. The start codon

Scanning usually stops at the first AUG in a favorable context, a short consensus around the AUG described by Marilyn Kozak in the 1980s and still called the Kozak sequence. AUG codes for methionine, which is why most newly made proteins begin with it (it is often trimmed off later).

4. The coding sequence

This is the part that spells out the protein. The four RNA bases (A, U, G, C) make 64 possible three-letter codons. Sixty-one of them specify amino acids, and since there are only 20 standard amino acids, most amino acids have several codons. Three codons, UAA, UAG and UGA, mean stop. It is read in one fixed frame from the start codon, so deleting a single base shifts every codon after it, which is why small insertions and deletions can be so damaging.

5. The stop codon and the 3' untranslated region (3' UTR)

After the stop codon the ribosome releases the finished protein and falls off, but the message continues. The 3' UTR is often longer than the 5' UTR and carries much of the message's instructions about itself: binding sites for microRNAs that silence it, sequences rich in A and U that mark it for fast turnover, signals that send it to a particular spot in the cell (a growing nerve fiber, for example). Near its end sits the signal, usually AAUAAA, that tells the cell where to cut and add the tail.

6. The poly(A) tail

The last part is a run of adenine bases added without any DNA template. Long-read sequencing studies indicate mammalian mRNAs are made with tails of roughly 200 to 250 adenines, which are trimmed over the message's life, often settling at around 100 or fewer. Poly(A)-binding proteins coat the tail and also contact proteins bound at the cap, looping the message into a circle that favors repeated rounds of translation. As the tail shortens, the loop weakens; once it falls below a threshold the cap is removed and the message is degraded.

mRNA vs tRNA vs rRNA

mRNA is only one of three RNA types that make protein synthesis work. In fact it is a small share of a cell's RNA by mass. Ribosomal RNA makes up most of it, and transfer RNA much of the rest.

The cleanest way to hold the mRNA vs tRNA difference in your head: mRNA is the sentence, tRNA is the dictionary. Each tRNA has a three-base anticodon that pairs with a codon on the mRNA, and it carries the amino acid that codon stands for. Enzymes called aminoacyl-tRNA synthetases attach the right amino acid to the right tRNA, and they are the real translators of the genetic code. Pairing at the third codon position is looser ("wobble"), which lets one tRNA read more than one codon.

rRNA, meanwhile, is not just scaffolding. The reaction that links one amino acid to the next is catalyzed by RNA in the ribosome's core, a finding confirmed by the atomic structures that earned Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath the 2009 Nobel Prize in Chemistry.

The life of a message

1. Transcription. In the nucleus, RNA polymerase II copies a gene into a precursor RNA. The cap is added within moments, while the strand is still being made.
2. Splicing. Most human genes are interrupted by introns, stretches that are not part of the final message. A large RNA and protein machine, the spliceosome, cuts them out and joins the remaining exons. Many genes can be spliced in more than one way, so one gene can give several related proteins.
3. Tail and export. The precursor is cut at the 3' end, the poly(A) tail is added, and the mature mRNA is exported through pores in the nuclear membrane.
4. Translation. Ribosomes load at the cap and scan to the start codon. Several ribosomes often work on one message at once, spaced along it like beads, a structure called a polysome.
5. Quality control. A message with a premature stop codon is usually caught and destroyed by a surveillance pathway called nonsense-mediated decay, which limits the damage from faulty copies.
6. Decay. The tail shortens, the cap comes off and enzymes break the message down. Lifetimes vary widely from one gene to the next.

Bacteria do it differently. Their mRNA has no cap or stabilizing tail, one message can code for several proteins in a row, and with no nucleus in the way, ribosomes start reading while the RNA is still being made. Bacterial messages usually last only minutes.

Synthetic mRNA: vaccines and medicines

Because a cell will translate any well-formed message it is given, an mRNA made in a test tube can instruct cells to make a chosen protein for a while. The synthetic versions copy the natural structure part for part: a cap, UTRs chosen for stability and efficient translation, a coding sequence for the target protein, and a poly(A) tail.

Two problems held the approach back for years. Synthetic RNA set off innate immune alarms, and it was destroyed before it reached cells. Katalin Karikó and Drew Weissman showed that swapping uridine for modified versions of it greatly reduced the immune reaction, work recognized with the 2023 Nobel Prize in Physiology or Medicine. Packaging the RNA in lipid nanoparticles, tiny fat droplets that fuse with cells, solved much of the delivery problem.

What is approved in the US: mRNA vaccines against COVID-19, first authorized for emergency use in December 2020 and later licensed by the FDA (Comirnaty in 2021, Spikevax in 2022), and an mRNA vaccine against RSV (mRESVIA), approved in May 2024 as the first mRNA vaccine for a disease other than COVID-19. Public health agencies including the CDC explain that vaccine mRNA works in the cytoplasm, does not enter the nucleus where DNA is kept, does not change a person's DNA, and is broken down by the cell after use.

What is still in trials: personalized cancer vaccines, in which mRNA encodes fragments of mutated proteins found in a patient's own tumor, are being tested, including in phase 3 trials in melanoma. Researchers are also testing mRNA to replace missing enzymes in some rare diseases. You can look these studies up yourself; our guide on how to read a ClinicalTrials.gov listing shows what to check, and our page on how lab discoveries reach the clinic explains why the gap between a good idea and an approved product is so long.

Laboratories use synthetic mRNA too. In 2010, researchers showed that modified mRNAs for the reprogramming factors could turn human skin cells into induced pluripotent stem cells without inserting anything into the cells' DNA, a route still used to make cleaner cell lines.

If you want the human story behind the vaccine work, Walter Isaacson's The Code Breaker is mostly about CRISPR and Jennifer Doudna, but its closing section follows the 2020 rush to build COVID-19 vaccines, RNA ones included. We suggest books based on their contents and published reviews.

Bench reading

• The Gene: An Intimate History (Siddhartha Mukherjee)paperbackGenetics from Mendel's peas to genome editing, told with family history running through it.Open on Amazon
• The Song of the Cell (Siddhartha Mukherjee)hardcoverA history of the cell and of the therapies built on it, from blood transfusion to cell therapy.Open on Amazon

Picked from specifications, manuals and published reviews; we have not tested these items ourselves. As an Amazon Associate I earn from qualifying purchases. All our bench picks

Quick questions

Is mRNA the same as DNA?

No. DNA is double-stranded, uses the sugar deoxyribose and the base thymine, and is kept long term. mRNA is single-stranded, uses ribose and uracil in place of thymine, and is temporary by design.

What are the parts of mRNA structure, in order?

The 5' cap, the 5' UTR, the start codon, the coding sequence, the stop codon, the 3' UTR and the poly(A) tail. If an exam asks for the parts that are translated, the answer is only the coding sequence, from the start codon to the codon before the stop.