intron
Summary
Introns are non-coding sequences within a gene that are transcribed into pre-mRNA but removed via splicing before translation, leaving only exons to form mature mRNA. Alternative splicing of exons (facilitated by intron removal) allows a single gene to produce multiple protein isoforms, increasing proteomic diversity.
Detail
Introns (intervening sequences) are DNA/RNA segments within eukaryotic genes that interrupt the protein-coding exons. During transcription, RNA polymerase II produces heterogeneous nuclear RNA (hnRNA/pre-mRNA) containing both exons and introns. The spliceosome—composed of small nuclear ribonucleoproteins (snRNPs: U1, U2, U4, U5, U6) and associated proteins—recognizes conserved sequences at intron boundaries: the 5' GU donor site, the 3' AG acceptor site, and an internal branch point adenosine. Splicing proceeds via two transesterification reactions forming a lariat intermediate, excising the intron and ligating adjacent exons.
Clinical relevance: Mutations at splice sites (e.g., disrupting GU-AG consensus sequences) can cause exon skipping or intron retention, leading to aberrant mRNA and disease—classic examples include certain forms of beta-thalassemia (splice site mutations in the beta-globin gene) and some cases of cystic fibrosis. Alternative splicing (differential inclusion/exclusion of exons) is a key mechanism for generating protein diversity from a limited number of genes and is regulated by splicing factors; dysregulation is implicated in cancers and neurodegenerative diseases (e.g., tau splicing in frontotemporal dementia).
Introns also have regulatory roles—some contain enhancer elements, microRNAs, or snoRNAs. The number and size of introns vary widely between genes and organisms; prokaryotes generally lack introns (their genes are typically continuous), which is a key distinguishing feature from eukaryotic gene structure tested on boards. Understanding intron/exon boundaries is essential for interpreting genetic mutations classified as splice-site mutations versus missense/nonsense mutations, which is frequently tested in USMLE genetics questions.
Sources
- First Aid for the USMLE Step 1
- Molecular Biology of the Cell (Alberts et al.)
- Lippincott Illustrated Reviews: Biochemistry
- Robbins and Cotran Pathologic Basis of Disease
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.