Role of the ATP-dependent chromatin remodeling enzyme Fun30/Smarcad1 in the regulation of mRNA splicing.

Role of the ATP-dependent chromatin remodeling enzyme Fun30/Smarcad1 in the regulation of mRNA splicing.
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ATP 依赖性染色质重塑酶 Fun30/Smarcad1 在 mRNA 剪接调节中的作用。

DOI:
10.1016/j.bbrc.2020.02.175
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发表时间:
2020
影响因子:
3.1
通讯作者:
Wu,Wei-Hua
Wu,Wei-Hua
中科院分区:
生物学4区
文献类型:
--
作者:
Niu,Qiankun;Wang,Wei;Wei,Zhe;Byeon,Boseon;Das,AsimBikas;Chen,Bo-Shiun;Wu,Wei-Hua

文献摘要

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酵母依赖于ATP的染色质重塑酶Fun30已被证明调节异染色质沉默、DNA修复、转录和染色质组织。尽管染色质结构被认为影响剪接位点的识别和调控,但依赖于ATP的染色质重塑酶是否在剪接调控中发挥作用尚不清楚。在这项研究中,我们发现在Fun30耗尽的细胞中,前mRNA的剪接效率受到损害,剪接体的招募受到影响。此外,Fun30还富含于单个内含子基因的基因体中。此外,我们还发现,Pre-mRNA剪接效率依赖于Fun30的染色质重塑活性。Fun30在剪接中的功能进一步得到了以下观察的支持,即Fun30的哺乳动物同源物Smarcad1调节选择性剪接。综上所述,这些结果为Fun30在调控剪接中的新作用提供了证据。
The yeast ATP-dependent chromatin remodeling enzyme Fun30 has been shown to regulate heterochromatin silencing, DNA repair, transcription, and chromatin organization. Although chromatin structure has been proposed to influence splice site recognition and regulation, whether ATP-dependent chromatin remodeling enzyme plays a role in regulating splicing is not known. In this study, we find that pre-mRNA splicing efficiency is impaired and the recruitment of spliceosome is compromised in Fun30-depleted cells. In addition, Fun30 is enriched in the gene body of individual intron-containing genes. Moreover, we show that pre-mRNA splicing efficiency is dependent on the chromatin remodeling activity of Fun30. The function of Fun30 in splicing is further supported by the observation that, Smarcad1, the mammalian homolog of Fun30, regulates alternative splicing. Taken together, these results provide evidence for a novel role of Fun30 in regulating splicing.