Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing.
Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing.
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酵母 TRAMP 复合物与内含子序列的共转录募集促进了最佳的前 mRNA 剪接
DOI：
10.1093/nar/gkt888
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Wong CM
中科院分区：
文献类型：
--
作者：
Kong KY;Tang HM;Pan K;Huang Z;Lee TH;Hinnebusch AG;Jin DY;Wong CM
真核细胞细胞核中的大多数不需要的RNA转录本，如剪接缺陷的前mRNAs和剪接出的内含子，都会被核外切体迅速降解。在萌芽酵母中，许多这些不需要的RNA转录本，包括剪接出的内含子，在随后的核外切体介导的降解之前，首先被核外体辅因子Trf4/5p-Air1/2p-MTR4p聚腺苷酸化(TRAMP)复合体识别。然而，目前尚不清楚TRAMP何时识别剪接出的内含子，以及TRAMP是否在前mRNA剪接中具有潜在的作用。在这里，我们证明了TRAMP是以共转录的方式招募到新生的RNA转录本中，并在内含子序列上特别丰富。即使在核外切体活性缺陷的酵母菌株中，TRAMP组分的缺失也会导致未剪接前mRNAs的进一步积累，这表明TRAMP在剪接中具有新的刺激作用。我们还发现了TraMP和几个剪接因子之间新的遗传和物理相互作用，并进一步表明TraMP是剪接因子Msl5p的最佳招募所必需的。我们的研究提供了第一个证据，证明TRAMP促进了前mRNA的剪接，我们将其解释为一种故障安全机制，以确保在剪接之前或剪接过程中TRAMP的共转录招募，为随后的靶向剪接出的内含子快速被核外体降解做准备。
Most unwanted RNA transcripts in the nucleus of eukaryotic cells, such as splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts, including spliced-out introns, are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. However, it remains unclear when spliced-out introns are recognized by TRAMP, and whether TRAMP may have any potential roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is cotranscriptionally recruited to nascent RNA transcripts, with particular enrichment at intronic sequences. Deletion of TRAMP components led to further accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We also uncovered new genetic and physical interactions between TRAMP and several splicing factors, and further showed that TRAMP is required for optimal recruitment of the splicing factor Msl5p. Our study provided the first evidence that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe mechanism to ensure the cotranscriptional recruitment of TRAMP before or during splicing to prepare for the subsequent targeting of spliced-out introns to rapid degradation by the nuclear exosome.
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