Post-Transcriptional Modifications

Key vocabulary terms and definitions covering post-transcriptional RNA processing steps and clinical correlations.

Post-Transcriptional Modifications

Processing events after transcription that convert a primary RNA transcript (pre-mRNA/hnRNA) into mature, functional mRNA.

hnRNA / pre-mRNA

Primary transcript, heterogeneous nuclear RNA (hnRNA), also called pre-mRNA, from which mature mRNA is derived.

5' Cap

A methylguanosine cap added to the 5' end of RNA; protects from degradation, helps ribosome binding (via eIF4E), aids nuclear export, and enhances splicing of the first intron.

Polyadenylation (Poly(A) Tail Addition)

Addition of up to ~250 adenines by poly(A) polymerase; involves a polyadenylation signal (AAUAAA) near the 3' end and cleavage ~20 nucleotides downstream by an endonuclease.

Poly(A) Tail Functions

Increases mRNA stability, facilitates export to the cytoplasm, enhances translation efficiency, and supports ribosome recycling.

Splicing

Removal of introns and joining of exons in the pre-mRNA to produce mature mRNA.

Spliceosome

Large RNA–protein complex that catalyzes splicing; composed of snRNPs (U1, U2, U4, U5, U6) and proteins.

5' Splice Site

The GU sequence at the 5' end of an intron recognized by U1 snRNP.

Lariat Formation

Branch point A attacks the 5' splice site to form a lariat; the 3' splice site is cleaved and exons are ligated, yielding mature mRNA.

Alternative Splicing

Cell-specific regulation of splice-site accessibility, producing different transcript variants and protein products from the same gene.

Exon

Coding sequences that remain in the mature mRNA after splicing.

Intron

Noncoding sequences removed during splicing.

RNA Editing

Post-transcriptional base modifications of RNA; enzymes involved include ADARs and APOBECs; includes A-to-I and C-to-U edits.

ADARs

Adenosine Deaminases Acting on RNA; enzymes that convert adenosine to inosine in RNA.

APOBECs

Apolipoprotein B mRNA Editing Catalytic Polypeptide enzymes; mediate C-to-U edits in RNA.

A-to-I Editing

Adenosine to inosine RNA editing; inosine is read as guanosine, affecting codons and receptor mRNAs.

C-to-U Editing

Cytidine to uridine RNA editing; example includes APOB mRNA editing converting apoB-100 to apoB-48 in the intestine.

apoB-100 / apoB-48

Two protein isoforms produced by C-to-U editing of APOB mRNA; apoB-48 is produced in the intestine.

Spinal Muscular Atrophy (SMN1 mutations)

Neurodegenerative disease caused by SMN1 gene mutations; linked to splicing factor dysfunction affecting motor neurons.

Beta-thalassemia via faulty poly(A) signal

Disease arising from defective polyadenylation signal leading to unstable or reduced mRNA.

Cordycepin

Major bioactive agent in Cordyceps militaris that reduces poly(A) tail lengths of some mRNAs.

Cordyceps militaris

Fungus used in traditional Chinese medicine; source of cordycepin.

Myotonic Dystrophy Type 1

Disease caused by expansion of CTG repeats in the 3' UTR of the DMPK gene; toxic RNA sequesters splicing factors (MBNL family), altering splicing.

3' UTR CTG Repeats

CTG repeat expansion in the 3' untranslated region contributing to myotonic dystrophy type 1.