Prp8: Difference between revisions
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Following suite with its unique structural makeup, Prp8 also possesses the potential to perform a variety of functions at the heart of the spliceosome. Above all else, Prp8 has been strongly implicated as a large scaffold which coordinates the active catalytic components of the spliceosome <ref name='Prp8: At the heart of the spliceosome'>DOI:10.1261/rna.2220705</ref>. Prp8 acts as a cofactor for RNA splicing because it is required for the formation of the active (complex B*) spliceosome and for subsequent first and second transesterification reactions <ref name='Prp8: At the heart of the spliceosome'>DOI:10.1261/rna.2220705</ref>. Prp8's bromodomain has been evolutionarily modified to recognize acetylated lysine residues, and given that many spliceosomal proteins are acetylated at lysine residues, it is likely that Prp8 mediates the assembly of spliceosome proteins and protein-RNA contacts through recognition of the lysine residues <ref name='Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase'>PMID:21441348 </ref>. One example of such an interaction is Prp8's bromodomain mediated contact with Snu114p, which is a GTPase involved in RNA remodeling during the catalytic cycle of splicing <ref name='Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase'>PMID:21441348 </ref>. | Following suite with its unique structural makeup, Prp8 also possesses the potential to perform a variety of functions at the heart of the spliceosome. Above all else, Prp8 has been strongly implicated as a large scaffold which coordinates the active catalytic components of the spliceosome <ref name='Prp8: At the heart of the spliceosome'>DOI:10.1261/rna.2220705</ref>. Prp8 acts as a cofactor for RNA splicing because it is required for the formation of the active (complex B*) spliceosome and for subsequent first and second transesterification reactions <ref name='Prp8: At the heart of the spliceosome'>DOI:10.1261/rna.2220705</ref>. Prp8's bromodomain has been evolutionarily modified to recognize acetylated lysine residues, and given that many spliceosomal proteins are acetylated at lysine residues, it is likely that Prp8 mediates the assembly of spliceosome proteins and protein-RNA contacts through recognition of the lysine residues <ref name='Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase'>PMID:21441348 </ref>. One example of such an interaction is Prp8's bromodomain mediated contact with Snu114p, which is a GTPase involved in RNA remodeling during the catalytic cycle of splicing <ref name='Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase'>PMID:21441348 </ref>. | ||
Prp8's reverse transcritase and RNase H-like domains are postulated to function as recognition, interaction, and handover domains for snRNAs catalytically active in the spliceosome and portions of the pre-mRNA substrate <ref name='Mechanism for aar2p function as a U5 snRNP assembly factor'>PMID:21764848</ref>. Crosslinking experiments have shown that U5 and U6 snRNAs, as well as the GU dinucleotide of the 5' splice site, polypyrimidine tract (close to the intron branch point), and the 3' splice site all interact with or close to the reverse transcriptase and RNase H-like domains of Prp8 which supports the scaffolding and coordination role of Prp8 in pre-mRNA splicing <ref name='Structure and function of an RNase H domain at the heart of the spliceosome'>DOI:10.1038/emboj.2008.209</ref><ref name='splicing factor prp8 governs u4/u6 rna unwinding'>PMID:10024880</ref><ref name='roles of prp8 protein in the assembly of splicing complexes'>PMID:1396567<ref>. | Prp8's modified reverse transcritase and RNase H-like domains are postulated to function as recognition, interaction, and handover domains for snRNAs catalytically active in the spliceosome and portions of the pre-mRNA substrate <ref name='Mechanism for aar2p function as a U5 snRNP assembly factor'>PMID:21764848</ref>. Crosslinking experiments have shown that U5 and U6 snRNAs, as well as the GU dinucleotide of the 5' splice site, polypyrimidine tract (close to the intron branch point), and the 3' splice site all interact with or close to the reverse transcriptase and RNase H-like domains of Prp8 which supports the scaffolding and coordination role of Prp8 in pre-mRNA splicing <ref name='Structure and function of an RNase H domain at the heart of the spliceosome'>DOI:10.1038/emboj.2008.209</ref><ref name='splicing factor prp8 governs u4/u6 rna unwinding'>PMID:10024880</ref><ref name='roles of prp8 protein in the assembly of splicing complexes'>PMID:1396567<ref>. | ||
