MRNA structure, post-transcriptional modifications (cap, poly A, splicing).

Messenger RNA (mRNA) is a type of RNA that serves as the intermediate template between DNA and protein synthesis. It carries genetic information transcribed from genes and is translated by ribosomes into a specific amino acid sequence. In eukaryotes, primary mRNA (pre-mRNA) undergoes several essential **post-transcriptional modifications** before becoming a mature, translatable molecule.

Structure of mRNA

A typical eukaryotic mature mRNA molecule consists of the following regions:

• 5′ cap – A modified guanine nucleotide added to the 5′ end.
• 5′ untranslated region (5′ UTR) – Regulates translation initiation.
• Coding region (ORF) – Contains codons that encode the amino acid sequence.
• 3′ untranslated region (3′ UTR) – Involved in regulation of translation and mRNA stability.
• Poly(A) tail – A stretch of adenine nucleotides at the 3′ end.

• MRNA structure en.svg

  Structure of a mature eukaryotic mRNA

• Pre-mRNA processing diagram.svg

  Post-transcriptional modifications

Post-transcriptional modifications

Eukaryotic pre-mRNA (hnRNA) undergoes the following key modifications:

1. 5′ capping

• A 7-methylguanosine (m⁷G) cap is added to the 5′ end of the pre-mRNA shortly after transcription begins.
• **Enzymes involved:**
  • RNA triphosphatase
  • Guanylyltransferase
  • Methyltransferase

• **Functions:**
  • Protects mRNA from degradation by exonucleases.
  • Aids in ribosome binding during translation initiation.
  • Facilitates nuclear export of mRNA.

2. Polyadenylation (Poly(A) tail)

• After transcription, ~200 adenine nucleotides are added to the 3′ end by **poly(A) polymerase**.
• Requires cleavage of the pre-mRNA at a specific polyadenylation signal (AAUAAA).

• **Functions:**
  • Enhances mRNA stability.
  • Promotes translation efficiency.
  • Involved in nuclear export.

3. RNA splicing

• Removes non-coding sequences (**introns**) and joins coding sequences (**exons**).
• Carried out by the **spliceosome**, a large complex of small nuclear RNAs (snRNAs) and proteins (snRNPs).

• **Steps:**

1. Spliceosome recognizes 5′ and 3′ splice sites.
2. A lariat structure is formed from the intron.
3. Exons are ligated, and the intron is released and degraded.

• **Alternative splicing:**
  • Allows a single gene to code for multiple protein isoforms.
  • Increases protein diversity.

Summary table

Modification	Enzyme/Complex	Function
5′ capping	Guanylyltransferase, methyltransferase	Protects mRNA, promotes translation
Polyadenylation	Poly(A) polymerase	Stabilizes mRNA, aids in translation
Splicing	Spliceosome (snRNPs)	Removes introns, joins exons

Prokaryotic vs. eukaryotic mRNA

Feature	Eukaryotic mRNA	Prokaryotic mRNA
5′ cap	Present	Absent
Poly(A) tail	Present	Rare or absent
Introns	Present (spliced out)	Absent
Monocistronic/polysistronic	Mostly monocistronic	Often polycistronic

Clinical relevance

• **Splicing errors** – Mutations at splice sites can lead to diseases such as β-thalassemia, spinal muscular atrophy, and certain cancers.
• **mRNA vaccines** – Use modified mRNA with synthetic caps and poly(A) tails to encode antigens (e.g., COVID-19 vaccines).
• **Cancer therapeutics** – Targeting aberrant splicing patterns is a novel strategy in oncology.

References

Related articles

• Transcription
• RNA polymerase II
• Spliceosome
• RNA processing
• mRNA stability
• Translation (genetics)

Literature

• ALBERTS, Bruce. Molecular Biology of the Cell. 6. edition. New York : Garland Science, 2015. 338–355 pp. ISBN 978-0-8153-3218-3.

• BERG, Jeremy M. – TYMOCZKO, John L.. Biochemistry. 8. edition. New York : W.H. Freeman, 2015. 817–830 pp. ISBN 978-1-4641-2610-7.