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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Liu L,Query CC,Konarska MMdoi
10.1038/nsmb1240subject
Has Abstractpub_date
2007-06-01 00:00:00pages
519-26issue
6eissn
1545-9993issn
1545-9985pii
nsmb1240journal_volume
14pub_type
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