Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex.
Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex.
复制标题
DOI：
10.1186/s13072-021-00382-y
复制
发表时间：
2021-01-19
影响因子：
3.9
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Weigt M;Gao Q;Ban H;He H;Mastrobuoni G;Kempa S;Chen W;Li F
剪接因子最近被证明参与异染色质的形成，但它们在控制异染色质结构和功能方面的作用仍然知之甚少。在这项研究中，我们确定了人类剪接因子RBM10的裂殖酵母同源物，该同源物与TARP综合征有关。Rbm10在裂殖酵母中的过表达导致强的全局内含子保留。Rbm10还与剪接因子以类似于人RBM10的模式相互作用，表明Rbm10作为剪接调节因子的功能是保守的。令人惊讶的是，我们的深度测序数据显示，Rbm10的缺失对全基因组基因表达和剪接的影响很小。然而，突变体显示严重的异染色质缺陷。进一步的分析表明，突变体中的异染色质缺陷不是由异染色质因子的错误剪接引起的。我们的蛋白质组学数据显示，Rbm10协会与组蛋白去乙酰化酶Clr6复合物和染色质重塑已知是重要的异染色质沉默。Rbm10的缺失导致异染色质中Clr6的显著减少。我们的工作与以前的研究结果进一步表明，不同的剪接亚基可能在异染色质调控中发挥不同的作用。
Splicing factors have recently been shown to be involved in heterochromatin formation, but their role in controlling heterochromatin structure and function remains poorly understood. In this study, we identified a fission yeast homologue of human splicing factor RBM10, which has been linked to TARP syndrome. Overexpression of Rbm10 in fission yeast leads to strong global intron retention. Rbm10 also interacts with splicing factors in a pattern resembling that of human RBM10, suggesting that the function of Rbm10 as a splicing regulator is conserved. Surprisingly, our deep-sequencing data showed that deletion of Rbm10 caused only minor effect on genome-wide gene expression and splicing. However, the mutant displays severe heterochromatin defects. Further analyses indicated that the heterochromatin defects in the mutant did not result from mis-splicing of heterochromatin factors. Our proteomic data revealed that Rbm10 associates with the histone deacetylase Clr6 complex and chromatin remodelers known to be important for heterochromatin silencing. Deletion of Rbm10 results in significant reduction of Clr6 in heterochromatin. Our work together with previous findings further suggests that different splicing subunits may play distinct roles in heterochromatin regulation.
登录
查看更多内容
影响因子：
16
作者：
Dong, Qianhua;Yin, Feng-Xiang;Gao, Feng;Shen, Yuan;Zhang, Faben;Li, Yang;He, Haijin;Gonzalez, Marlyn;Yang, Jinpu;Zhang, Shu;Su, Min;Chen, Yu-Hang;Li, Fei
通讯作者：
Li, Fei
影响因子：
5.3
作者：
Agafonov, Dmitry E.;Deckert, Jochen;Luehrmann, Reinhard
通讯作者：
Luehrmann, Reinhard
影响因子：
3.7
作者：
Gonzalez, Marlyn;Li, Fei
通讯作者：
Li, Fei
影响因子：
16
作者：
Hegele, Anna;Kamburov, Atanas;Stelzl, Ulrich
通讯作者：
Stelzl, Ulrich
影响因子：
11.4
作者：
Buscaino, Alessia;Lejeune, Erwan;Allshire, Robin C.
通讯作者：
Allshire, Robin C.