Multiple functions of Saccharomyces cerevisiae splicing protein Prp24 in U6 RNA structural rearrangements

U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3' end. The 3' stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing....

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Bibliographic Details
Published in:	Genetics (Austin) Vol. 153; no. 3; pp. 1205 - 1218
Main Authors:	Vidaver, R.M, Fortner, D.M, Loos-Austin, L.S, Brow, D.A
Format:	Journal Article
Language:	English
Published:	United States Genetics Soc America 01-11-1999
Subjects:	alternative splicing Amino Acid Sequence Base Sequence binding proteins Conserved Sequence extragenic suppressors inhibitor genes messenger RNA Models, Molecular molecular conformation Molecular Sequence Data Mutagenesis, Site-Directed mutation Nucleic Acid Conformation phenotype precursors protein secondary structure Protein Structure, Secondary Recombinant Proteins - chemistry Recombinant Proteins - metabolism Ribonucleoproteins, Small Nuclear - chemistry Ribonucleoproteins, Small Nuclear - genetics Ribonucleoproteins, Small Nuclear - metabolism RNA RNA Splicing RNA, Fungal - chemistry RNA, Fungal - genetics RNA, Small Nuclear - chemistry RNA, Small Nuclear - genetics RNA-Binding Proteins - chemistry RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - growth & development Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Sequence Alignment Sequence Homology, Amino Acid spliceosomal rna spliceosomes Suppression, Genetic suppressor mutations
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Summary:	U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3' end. The 3' stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing. A mutation in yeast U6 RNA that hyperstabilizes the 3' stem confers cold sensitivity and inhibits U4/U6 assembly as well as a later step in splicing. Here we show that extragenic suppressors of the 3' stem mutation map to the gene coding for splicing factor Prp24. The suppressor mutations are located in the second and third of three RNA-recognition motifs (RRMs) in Prp24 and are predicted to disrupt RNA binding. Mutations in U6 RNA predicted to destabilize a novel helix adjacent to the 3' stem also suppress the 3' stem mutation and enhance the growth defect of a suppressor mutation in RRM2 of Prp24. Both phenotypes are reverted by a compensatory mutation that restores pairing in the novel helix. These results are best explained by a model in which RRMs 2 and 3 of Prp24 stabilize an extended intramolecular structure in U6 RNA that competes with the U4/U6 RNA interaction, and thus influence both association and dissociation of U4 and U6 RNAs during the splicing cycle.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0016-6731 1943-2631 1943-2631
DOI:	10.1093/genetics/153.3.1205