## The Spliceosome and Intron Removal ### The Spliceosome Complex **Key Point:** The spliceosome is a massive ribonucleoprotein complex composed of five small nuclear RNAs (snRNAs: U1, U2, U4, U5, U6) and associated proteins (~150 proteins total). It is the molecular machine responsible for pre-mRNA splicing. ### Mechanism of Splicing 1. **Assembly** - snRNPs and proteins assemble on the pre-mRNA at splice sites - U1 snRNP binds the 5' splice site (GU sequence) - U2 snRNP binds the branch point (typically UACUAAC) - U4/U6•U5 tri-snRNP complex joins to form the catalytic core 2. **Catalytic steps** (two transesterification reactions) - First cut: 5' splice site is cleaved; 3'-OH of upstream exon attacks the branch point adenosine - Second cut: 3' splice site is cleaved; 5'-OH of downstream exon attacks the 3'-OH of upstream exon - Intron is released as a lariat structure ### Cofactor Requirements | Cofactor | Role | |----------|------| | **Mg²⁺** | Essential for catalytic activity; stabilizes RNA-protein interactions and transition states | | **ATP** | Required for spliceosome assembly, conformational changes, and catalytic activation | | **GTP** | Some sources cite GTP as an alternative or supplementary energy source | **High-Yield:** The spliceosome is a **self-splicing ribozyme** in the sense that the snRNAs (particularly U2 and U6) catalyze the transesterification reactions; proteins provide structural support and regulation. **Mnemonic:** **SNRP-CAT** = SNRPs + Proteins catalyze; Cofactors Are Mg²⁺ and ATP ### Why This Is Tested Splicing is a fundamental eukaryotic gene expression step. Defects in splicing are implicated in ~15% of human genetic diseases (e.g., spinal muscular atrophy, β-thalassemia). [cite:Molecular Biology of the Gene 8e Ch 15]
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