Nonsense-mediated mRNA decay mutes the splicing defects of spliceosome component mutations
Nonsense-mediated mRNA decay mutes the splicing defects of spliceosome component mutations
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DOI：
10.1261/rna.1736809
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发表时间：
2009-12-01
期刊：
影响因子：
4.5
通讯作者：
Chanfreau, Guillaume F.
中科院分区：
文献类型：
--
作者：
Kawashima, Tadashi;Pellegrini, Matteo;Chanfreau, Guillaume F.
许多剪接因子在前 mRNA 剪接中的作用以及这些因子在特定转录本加工中的参与通常通过体内功能丧失突变体的分析来确定。在这里，我们表明，失活无义介导的 mRNA 衰减 (NMD) 会导致与几种酿酒酵母剪接因子突变相关的剪接表型增强。平铺微阵列显示，prp17 Delta 和 prp18 Delta 突变株中 NMD 因子 Upf1p 的失活会导致比在单个突变体中观察到的更大范围的剪接缺陷，包括先前显示不受 Prp17p 或 Prp18p 失活影响的新转录本。第二步/循环因子 prp22-1 突变体以及 nam8 Delta 和 mud1 Delta U1 snRNP 成分突变体中 Upf1p 的失活也会增加几种特定转录本的未剪接前体积累。此外，UPF1的缺失部分抑制了与prp17 Delta或prp22-1突变相关的生长缺陷，证明了NMD和剪接因子突变体之间存在积极的遗传相互作用。这些结果表明，NMD 的 RNA 监测可以掩盖剪接因子突变的一些影响，并且除非降解未剪接前体的 RNA 降解系统也失活，否则在体内剪接因子的作用无法被完全理解。
The role of many splicing factors in pre-mRNA splicing and the involvement of these factors in the processing of specific transcripts have often been defined through the analysis of loss-of-function mutants in vivo. Here we show that inactivating the nonsense-mediated mRNA decay (NMD) results in an enhancement of splicing phenotypes associated with several S. cerevisiae splicing factor mutations. Tiling microarrays showed that inactivation of the NMD factor Upf1p in the prp17 Delta and prp18 Delta mutant strains results in a larger spectrum of splicing defects than what is observed in the single mutants, including new transcripts previously shown unaffected by Prp17p or Prp18p inactivation. Inactivation of Upf1p in the second step/recycling factor prp22-1 mutant and in the nam8 Delta and mud1 Delta U1 snRNP component mutants also increase unspliced precursor accumulation of several specific transcripts. In addition, deletion of UPF1 partially suppresses the growth defects associated with the prp17 Delta or prp22-1 mutations, demonstrating a positive genetic interaction between NMD and splicing factor mutants. These results show that RNA surveillance by NMD can mask some of the effects of splicing factor mutations, and that the roles of splicing factors cannot be fully understood in vivo unless RNA degradation systems that degrade unspliced precursors are also inactivated.