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SR 蛋白 Npl3 是酿酒酵母减数分裂剪接调控网络的必需组成部分。

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

机构信息

Department of Viticulture and Enology, University of California Davis, Davis, CA, USA.

出版信息

Nucleic Acids Res. 2021 Mar 18;49(5):2552-2568. doi: 10.1093/nar/gkab071.

Abstract

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.

摘要

酿酒酵母减数分裂中的基因表达程序涉及通过多个剪接激活因子(例如 Mer1、Nam8、Tgs1)对减数分裂特异性基因进行调节剪接。在这里,我们表明,SR 蛋白 Npl3 是减数分裂剪接调控所必需的,并且对于减数分裂细胞周期的正确执行也是必不可少的。尽管在有丝分裂中缺失 Npl3 并不影响生存能力,但它会导致减数分裂特异性转录本中的内含子保留、减数分裂双链断裂处理效率低下以及减数分裂细胞周期停滞。Npl3 的靶标在某些情况下与其他剪接调节剂重叠,而其具有独特的靶转录本,这些转录本是不共享的。在缺乏 Npl3 的情况下,通过将非共识剪接位点转换为共识序列,可挽救三个转录本(MER2、HOP2 和 SAE3)的剪接缺陷。进一步发现 Npl3 的甲基化是剪接 Mer1 依赖性转录本所必需的,这表明 Npl3 支持剪接的是特定于转录本的机制。这些数据共同确定了芽殖酵母 SR 蛋白 Npl3 在减数分裂中作为减数分裂剪接调控网络的一部分的重要功能。

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