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

Li Liu, Charles C. Query, Maria M. Konarska

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalNature Structural and Molecular Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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