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 language | English (US) |
---|---|
Pages (from-to) | 519-526 |
Number of pages | 8 |
Journal | Nature Structural and Molecular Biology |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2007 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology