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Rbm38 可减少由剪接缺陷引起的基因转录延伸缺陷。

Rbm38 Reduces the Transcription Elongation Defect of the Gene Caused by Splicing Deficiency.

机构信息

Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.

出版信息

Int J Mol Sci. 2020 Nov 20;21(22):8799. doi: 10.3390/ijms21228799.

Abstract

Pre-mRNA splicing is an essential mechanism for ensuring integrity of the transcriptome in eukaryotes. Therefore, splicing deficiency might cause a decrease in functional proteins and the production of nonfunctional, aberrant proteins. To prevent the production of such aberrant proteins, eukaryotic cells have several mRNA quality control mechanisms. In addition to the known mechanisms, we previously found that transcription elongation is attenuated to prevent the accumulation of pre-mRNA under splicing-deficient conditions. However, the detailed molecular mechanism behind the defect in transcription elongation remains unknown. Here, we showed that the RNA binding protein Rbm38 reduced the transcription elongation defect of the gene caused by splicing deficiency. This reduction was shown to require the N- and C-terminal regions of Rbm38, along with an important role being played by the RNA-recognition motif of Rbm38. These findings advance our understanding of the molecular mechanism of the transcription elongation defect caused by splicing deficiency.

摘要

前体 mRNA 剪接是真核生物确保转录组完整性的一种基本机制。因此,剪接缺陷可能导致功能性蛋白质减少和无功能、异常蛋白质的产生。为了防止产生这种异常蛋白质,真核细胞有几种 mRNA 质量控制机制。除了已知的机制外,我们之前还发现,转录延伸受到抑制,以防止在剪接缺陷条件下前体 mRNA 的积累。然而,转录延伸缺陷背后的详细分子机制仍不清楚。在这里,我们表明 RNA 结合蛋白 Rbm38 降低了剪接缺陷引起的 基因的转录延伸缺陷。这种减少需要 Rbm38 的 N 端和 C 端区域,以及 Rbm38 的 RNA 识别基序发挥重要作用。这些发现推进了我们对剪接缺陷引起的转录延伸缺陷的分子机制的理解。

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