Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing.

The spliceosome is thought to undergo a conformational change between the two catalytic steps of precursor messenger RNA splicing, although the specific events in this transition are poorly understood. We previously proposed a two-state model of splicing in which the conformations required for the first and second steps are in ...
competition. Here, we identify and characterize a class of prp8 mutants that suppress first-step splicing defects and oppose the action of the previously described prp8 suppressors of second-step defects; these opposing effects parallel those of ribosomal 'ram' and 'restrictive' mutants, which alter fidelity of transfer RNA decoding. On the basis of genetic interactions, we propose that prp8-mediated substrate repositioning during the transition occurs between catalytic-center opening and closure mediated by the U6 small nuclear RNA and the DExH/D ATPase gene prp16. Modulation of these events alters splice-site selection and splicing fidelity.
Mesh Terms:
Adenosine Triphosphatases, Alleles, DNA Primers, Models, Molecular, Mutation, Protein Conformation, RNA Helicases, RNA Splicing, RNA, Small Nuclear, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spliceosomes
Nat. Struct. Mol. Biol.
Date: Jun. 01, 2007
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