The SR-protein Npl3 is an essential component of the meiotic splicing regulatory network in Saccharomyces cerevisiae.

The SR-protein Npl3 is an essential component of the meiotic splicing regulatory network in Saccharomyces cerevisiae.
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DOI:
10.1093/nar/gkab071
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发表时间:
2021-03-18
影响因子:
14.9
通讯作者:
Montpetit B
Montpetit B
中科院分区:
生物学2区
文献类型:
--
作者:
Sandhu R;Sinha A;Montpetit B

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酿酒酵母的减数分裂基因表达程序涉及通过多个剪接激活子(如Mer1, Nam8, Tgs1)调节减数分裂特异性基因的剪接。在这里,我们表明SR蛋白Npl3是减数分裂剪接调节所必需的,并且对于减数分裂细胞周期的正确执行至关重要。Npl3的缺失虽然不是有丝分裂生存所必需的,但会导致减数分裂特异性转录物中的内含子保留,减数分裂双链断裂加工效率低下,并导致减数分裂细胞周期停滞。在某些情况下,Npl3的靶标与其他剪接调节因子重叠,同时也具有不共享的独特靶标转录本。在缺乏Npl3的情况下,三个转录本(MER2, HOP2和SAE3)的剪接缺陷通过将非一致剪接位点转化为一致序列来修复。进一步发现,Npl3的甲基化是剪接mer1依赖性转录物所必需的,这表明Npl3支持剪接的转录特异性机制。总之,这些数据确定了出芽酵母SR蛋白Npl3在减数分裂中作为减数分裂剪接调节网络的一部分的基本功能。
The meiotic gene expression program in Saccharomyces cerevisiae involves regulated splicing of meiosis-specific genes via multiple splicing activators (e.g. Mer1, Nam8, Tgs1). Here, we show that the SR protein Npl3 is required for meiotic splicing regulation and is essential for proper execution of the meiotic cell cycle. The loss of Npl3, though not required for viability in mitosis, caused intron retention in meiosis-specific transcripts, inefficient meiotic double strand break processing and an arrest of the meiotic cell cycle. The targets of Npl3 overlapped in some cases with other splicing regulators, while also having unique target transcripts that were not shared. In the absence of Npl3, splicing defects for three transcripts (MER2, HOP2 and SAE3) were rescued by conversion of non-consensus splice sites to the consensus sequence. Methylation of Npl3 was further found to be required for splicing Mer1-dependent transcripts, indicating transcript-specific mechanisms by which Npl3 supports splicing. Together these data identify an essential function for the budding yeast SR protein Npl3 in meiosis as part of the meiotic splicing regulatory network.
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