exon

**Definition:** Exons are "expressed" regions of a gene present in the mature mRNA. Introns ("intervening" regions) are transcribed into pre-mRNA but removed during splicing. Exons include the coding sequence and the 5' and 3' untranslated regions (UTRs).

**RNA processing (eukaryotes, nucleus):** - Pre-mRNA (hnRNA) is transcribed by RNA polymerase II. - 5' capping (7-methylguanosine) and 3' polyadenylation (poly-A tail, signaled by AAUAAA). - Splicing by the spliceosome: snRNPs (U1, U2, U4, U5, U6) complexed with proteins. Introns begin with GU and end with AG (GU-AG rule). A branch point adenine forms a lariat intermediate; the lariat intron is released and degraded. - Splicing is a two-step transesterification, and exons are ligated together.

**Alternative splicing:** Different exon combinations from one gene produce different mRNAs and protein isoforms. This increases proteome diversity (~20,000 genes yield many more proteins). Examples: membrane-bound vs. secreted IgM; tissue-specific tropomyosin isoforms.

**Clinical correlations:** - **Anti-Smith antibodies (SLE):** target snRNPs in the spliceosome. Anti-U1 RNP is seen in mixed connective tissue disease. - **Beta-thalassemia:** splice-site mutations in the β-globin gene cause abnormal splicing and reduced or absent β-globin. - **Duchenne muscular dystrophy:** frameshift deletions (often of exons) in the dystrophin gene (X-linked) cause a truncated, nonfunctional protein. Becker has in-frame deletions with partially functional dystrophin. Exon-skipping antisense oligonucleotides (e.g., eteplirsen) restore the reading frame. - **Nonsense, missense, frameshift mutations** within exons alter protein products. Silent mutations may still disrupt splicing. - **Spinal muscular atrophy:** SMN1 deletion; SMN2 differs in a single nucleotide that causes exon 7 skipping (nusinersen modulates splicing). - **Exome sequencing:** targets exons (~1–2% of the genome) and is useful for finding causative mutations in Mendelian disease.

**High-yield contrasts:** - Exons: retained, expressed. Introns: removed, often regulatory elements and ncRNAs. - Prokaryotes lack introns and the spliceosome, so they have no splicing; their mRNA is polycistronic. - Mature mRNA = 5' cap + exons + poly-A tail.