期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 14, 期 6, 页码 519-526出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb1240
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资金
- NIGMS NIH HHS [GM57829, GM49044, R01 GM057829-08, R01 GM057829] Funding Source: Medline
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.
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