Prp24: Difference between revisions

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Prp24 is a U6 snNRP protein that functions in the annealing of the U4 and U6 snRNPs during the assembly of the spliceosome. This protein was first identified in a genetic screen as mutated gene that caused an accumulation of pre-mRNA <ref name="Vij">PMID:2676722</ref>. Its first functional role was suggested after several mutant forms of the protein were found to suppress a cold sensitive growth defect caused by mutations in the U4 snRNA <ref name="Shannon">PMID:1827420</ref>. It is thought that Prp24 helps to stabilize the U6 snRNA and hold it in a conformation that promotes base pairing interactions with the U4 snRNA to form the stem I and stem II structures of the U4/U6 di-snRNP <ref name="Vidaver">PMID:10545453</ref>. Although Prp24 departs from the U4/U6 complex before the formation of the U4/U6.U5 tri-snRNP, it has been suggested that Prp24 may also play a role in the dissociation of U4 from U6 during the base pairing of U6 with U2 and the 5' splice site <ref name="Vaidya">Vaidya V, Vijayraghavan U. Prp21, a U2-snRNP-associated protein, and Prp24, a U6-snRNP-associated protein, functionally interact during spliceosome assembly. J Genet. 1998 Dec; 77(3):85-94</ref>. This additional role for Prp24, however, has not been sufficiently supported experimentally.

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U6 is arguably the most structurally dynamic snRNA involved in the splicing process, seemingly undergoing at least three different structures: it exists in one conformation as free U6 snRNP, another when base paired in the U4/U6 di-snRNP, and a third in base pairing interactions with U2 and the 5' splice site <ref name="Jandrositz"/>. One large role suggested for Prp24 has been in assisting in the conformational changes between the free U6 structure and the U4/U6 conformation.

Prp24 co-immunoprecipitates with free U6 and U4/U6 di-snRNP, indicating that it is closely associated with these particles <ref name="Shannon"/><ref name="Ghetti">PMID:7585243</ref>. Initial investigation revealed that Prp24 binds within the 30-56 nucleotide region of free U6, as well as to stem II of U4/U6 in the 39-56 and 67-70 nucleotide regions of U6 <ref name="Ghetti"/>. Further investigation of the structure showed that Prp24 very likely binds directly to the 40-43 nucleotides of U6 based on chemical modification of naked U6 snRNA compared to free U6 snRNP<ref name="Jandrositz"/>.

Prp24 co-immunoprecipitates with free U6 and U4/U6 di-snRNP, indicating that it is closely associated with these structures <ref name="Shannon"/><ref name="Ghetti">PMID:7585243</ref>. Initial investigation revealed that Prp24 binds within the 30-56 nucleotide region of free U6, as well as to stem II of U4/U6 in the 39-56 and 67-70 nucleotide regions of U6 <ref name="Ghetti"/>. Further investigation of the structure showed that Prp24 very likely binds directly to the 40-43 nucleotides of U6 based on chemical modification of naked U6 snRNA compared to free U6 snRNP<ref name="Jandrositz"/>.

The main function of Prp24 seems to be directly related to formation of the U4/U6 complex, particularly based on the evidence that Prp24 is present in U6 and U4/U6, but not U4/U6.U5 <ref name="Shannon"/><ref name="Ghetti"/><ref name="Jandrositz"/>. Prp24 greatly increases the rate and efficiency of U4/U6 annealing <ref name="Raghunathan">PMID:9452384</ref> and mutations in Prp24 have been shown to prevent the formation of the U4/U6 di-snRNP <ref name="Lygerou">PMID:10022888</ref>. Although the exact mechanism by which Prp24 promotes annealing of U4 and U6 is not known, it has been suggested that Prp24 may stabilize the secondary structure of U6 to allow it to interact with U4 in order to allow formation of U4/U6 <ref name="Vidaver"/>.

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 Prp24 is a U6 snNRP protein that functions in the annealing of the U4 and U6 snRNPs during the assembly of the spliceosome.  This protein was first identified in a genetic screen as mutated gene that caused an accumulation of pre-mRNA <ref name="Vij">PMID:2676722</ref>.  Its first functional role was suggested after several mutant forms of the protein were found to suppress a cold sensitive growth defect caused by mutations in the U4 snRNA <ref name="Shannon">PMID:1827420</ref>.  It is thought that Prp24 helps to stabilize the U6 snRNA and hold it in a conformation that promotes base pairing interactions with the U4 snRNA to form the stem I and stem II structures of the U4/U6 di-snRNP <ref name="Vidaver">PMID:10545453</ref>.  Although Prp24 departs from the U4/U6 complex before the formation of the U4/U6.U5 tri-snRNP, it has been suggested that Prp24 may also play a role in the dissociation of U4 from U6 during the base pairing of U6 with U2 and the 5' splice site <ref name="Vaidya">Vaidya V, Vijayraghavan U. Prp21, a U2-snRNP-associated protein, and Prp24, a U6-snRNP-associated protein, functionally interact during spliceosome assembly.  J Genet. 1998 Dec; 77(3):85-94</ref>.  This additional role for Prp24, however, has not been sufficiently supported experimentally.
@@ Line 50: / Line 51: @@
 U6 is arguably the most structurally dynamic snRNA involved in the splicing process, seemingly undergoing at least three different structures: it exists in one conformation as free U6 snRNP, another when base paired in the U4/U6 di-snRNP, and a third in base pairing interactions with U2 and the 5' splice site <ref name="Jandrositz"/>.  One large role suggested for Prp24 has been in assisting in the conformational changes between the free U6 structure and the U4/U6 conformation.
+Prp24 co-immunoprecipitates with free U6 and U4/U6 di-snRNP, indicating that it is closely associated with these particles <ref name="Shannon"/><ref name="Ghetti">PMID:7585243</ref>.  Initial investigation revealed that Prp24 binds within the 30-56 nucleotide region of free U6, as well as to stem II of U4/U6 in the 39-56 and 67-70 nucleotide regions of U6 <ref name="Ghetti"/>.  Further investigation of the structure showed that Prp24 very likely binds directly to the 40-43 nucleotides of U6 based on chemical modification of naked U6 snRNA compared to free U6 snRNP<ref name="Jandrositz"/>.
 <Structure load='2ghp' size='300' frame='true' align='right' caption='' scene='Sandbox_Reserved_340/2ghp/3'/>
-Prp24 co-immunoprecipitates with free U6 and U4/U6 di-snRNP, indicating that it is closely associated with these structures <ref name="Shannon"/><ref name="Ghetti">PMID:7585243</ref>.  Initial investigation revealed that Prp24 binds within the 30-56 nucleotide region of free U6, as well as to stem II of U4/U6 in the 39-56 and 67-70 nucleotide regions of U6 <ref name="Ghetti"/>.  Further investigation of the structure showed that Prp24 very likely binds directly to the 40-43 nucleotides of U6 based on chemical modification of naked U6 snRNA compared to free U6 snRNP<ref name="Jandrositz"/>.
 The main function of Prp24 seems to be directly related to formation of the U4/U6 complex, particularly based on the evidence that Prp24 is present in U6 and U4/U6, but not U4/U6.U5 <ref name="Shannon"/><ref name="Ghetti"/><ref name="Jandrositz"/>.  Prp24 greatly increases the rate and efficiency of U4/U6 annealing <ref name="Raghunathan">PMID:9452384</ref> and mutations in Prp24 have been shown to prevent the formation of the U4/U6 di-snRNP <ref name="Lygerou">PMID:10022888</ref>.  Although the exact mechanism by which Prp24 promotes annealing of U4 and U6 is not known, it has been suggested that Prp24 may stabilize the secondary structure of U6 to allow it to interact with U4 in order to allow formation of U4/U6 <ref name="Vidaver"/>.