Prp24

This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada.

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IntroductionIntroduction

Prp24Prp24

Prp24 (Pre-mRNA splicing Protein 24) is a Saccharomyces cerevisiae yeast protein that functions in the formation of base pair interactions between the U6 and U4 snRNPs (small nuclear ribonucleoproteins to form the U4/U6 di-snRNP in the assembly of the spliceosome. This protein is an octamer containing four RNA recognition motifs (RRMs) that function in the binding of Prp24 to U6 snRNA. These RRMs domains are conserved in structure and sequence in proteins orthologous to Prp24 in Homo sapiens and Schizosaccharomyces pombe, as well as in other proteins containing RRMs.

Pre-mRNA SplicingPre-mRNA Splicing

Pre-mRNA splicing is an essential process in eukaryotes that removes non-coding introns from a pre-mRNA transcript and splices coding exons together before the mRNA is exported from the nucleus for translation into a protein. Splicing requires five snRNPs (U1, U2, U4, U5, U6), several other proteins, and the input of energy from ATP. The U1 and U2 snRNPs assemble individually on the pre-mRNA transcript, while U4 and U6 form a U4/U6 di-snRNP before interacting with U5 to form a U4/U6.U5 tri-snRNP that interacts with U1 and U2 at the pre-mRNA transcript. U4 and U1 then depart, and after conformational changes and base pair formation with the pre-mRNA the remaining snRNPs form the catalytically active spliceosome. Two transesterification reactions then occur; the first reaction is the nucleophillic attack of the a phosphate group at the end of the 5' exon by the 2' hydroxyl of a specific adenosine at the branch point sequence of the intron. This is then followed by the nucleophillic attack of the phosphorous group linking the 3' exon to the intron by the 3' hydroxyl of the 5' exon. These splicing reactions, in addition to the addition of 7-methylguanosine 5' cap and a 3' polyadenosine tail, results in a mature mRNA transcript that can be exported from the nucleus and translated into protein.