Niu Qiankun, Wang Wei, Wei Zhe, Byeon Boseon, Das Asim Bikas, Chen Bo-Shiun, Wu Wei-Hua
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan ROC.
Biochem Biophys Res Commun. 2020 May 28;526(2):453-458. doi: 10.1016/j.bbrc.2020.02.175. Epub 2020 Mar 28.
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.
酵母中依赖ATP的染色质重塑酶Fun30已被证明可调节异染色质沉默、DNA修复、转录和染色质组织。虽然有人提出染色质结构会影响剪接位点的识别和调控，但依赖ATP的染色质重塑酶是否在调节剪接中发挥作用尚不清楚。在本研究中，我们发现，在缺失Fun30的细胞中，前体mRNA剪接效率受损，剪接体的募集也受到影响。此外，Fun30在单个含内含子基因的基因体内富集。而且，我们表明前体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以下观察结果的支持：Fun30的哺乳动物同源物Smarcad1可调节可变剪接。综上所述，这些结果为Fun30在调节剪接中的新作用提供了证据。
