Eukaryotic pre-mRNA - Edubirdie

University:
University of California, San Diego
Course:
BIMM 100 | Molecular Biology
Academic year:

2024
Views:

241

Pages:

1
Author:

customer-8930767

molecular steps of eukaryotic pre-mRNA splicing, including spliceosome assembly and the two transesterification reactions. Pre-mRNA splicing removes introns and ligates exons, catalyzed by the spliceosome—a dynamic ribonucleoprotein complex comprising five small nuclear RNAs (snRNAs: U1, U2, U4, U5, U6) and ~150 proteins. Splicing occurs at conserved sequences: 5’ splice site (GU), branch point adenine, and 3’ splice site (AG). Assembly: U1 snRNP binds the 5’ splice site via complementary base pairing; U2AF (auxiliary factor) binds the polypyrimidine tract and 3’ splice site. U2 snRNP binds the branch point, bulging out the branch adenine. The pre-formed U4/U6•U5 tri-snRNP joins, then U1 and U4 are released, activating U6 to pair with U2 and the 5’ splice site. This forms the active site. Catalysis proceeds via two transesterifications without ATP. Step 1: The 2’-OH of the branch adenine attacks the phosphate at the 5’ splice site, forming a lariat intermediate and freeing the 5’ exon. Step 2: The 3’-OH of the 5’ exon attacks the 3’ splice site, ligating exons and releasing the lariat intron. After splicing, the spliceosome disassembles, and the lariat intron is debranched and degraded. Alternative splicing (regulated by splicing factors like SR proteins and hnRNPs) allows one gene to produce multiple protein isoforms. Errors in splicing cause diseases (e.g., spinal muscular atrophy, ?thalassemia). Self-splicing introns (group I/II) demonstrate that RNA can catalyze splicing, supporting the RNA world hypothesis.

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