Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing
Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing
复制标题
DOI：
10.1038/nsmb1240
复制
发表时间：
2007-06-01
影响因子：
16.8
通讯作者：
Konarska, Maria M.
中科院分区：
文献类型：
--
作者：
Liu, Li;Query, Charles C.;Konarska, Maria M.
剪接体被认为在前体信使RNA剪接的两个催化步骤之间经历了构象变化，尽管这种转变中的具体事件知之甚少。我们之前提出了一种双态拼接模型，其中第一步和第二步所需的构象处于竞争状态。在这里，我们鉴定并表征了一类抑制第一步剪接缺陷的prp8突变体，并反对先前描述的prp8抑制子对第二步缺陷的作用；这些相反的影响与核糖体“ram”和“限制性”突变相似，它们改变了转移RNA解码的保真度。在遗传相互作用的基础上，我们提出prp8介导的底物重定位发生在U6小核RNA和DExH/D atp酶基因prp16介导的催化中心打开和关闭之间。这些事件的调节改变了剪接位点的选择和剪接的保真度。
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.