The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function.
The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function.
复制标题
DOI：
10.1038/s41598-018-26576-1
复制
发表时间：
2018-05-25
影响因子：
4.6
通讯作者：
Laribee RN
中科院分区：
文献类型：
--
作者：
Chen H;Sirupangi T;Wu ZH;Johnson DL;Laribee RN
Ccr 4-Not复合物控制RNA聚合酶II（Pol II）依赖性基因表达和蛋白酶体功能。Not 4泛素连接酶是一种Ccr 4-Not亚基，具有RING结构域和保守的RNA识别基序以及功能未知的C3 H1结构域（称为RRM-C结构域）。我们证明，虽然个别Not 4 RING或RRM-C突变体不能复制Not 4缺陷细胞中发现的蛋白酶体缺陷，但两者的突变都表现出Not 4功能丧失表型。转录组分析显示，Not 4 RRM-C影响Pol II调节基因的特定子集，包括参与转录延伸、细胞周期蛋白依赖性激酶调节的营养反应和核糖体生物合成的基因。Not 4 RING、RRM-C或RING/RRM-C突变导致这些基因的一个子集的Pol II结合普遍增加，但它们对基因表达的影响并不总是与Pol II募集相关，这表明Not 4通过其他机制调节它们的表达。有趣的是，我们发现，虽然Not 4 RRM-C对于Ccr 4-Not与RNA Pol II的结合是不稳定的，但Not 4 RING结构域是这些相互作用所必需的。总的来说，这些数据阐明了保守的Not 4 RRM-C和RING结构域在体内调节Ccr 4-Not依赖性功能中先前未知的作用。
The Ccr4-Not complex controls RNA polymerase II (Pol II) dependent gene expression and proteasome function. The Not4 ubiquitin ligase is a Ccr4-Not subunit that has both a RING domain and a conserved RNA recognition motif and C3H1 domain (referred to as the RRM-C domain) with unknown function. We demonstrate that while individual Not4 RING or RRM-C mutants fail to replicate the proteasomal defects found in Not4 deficient cells, mutation of both exhibits a Not4 loss of function phenotype. Transcriptome analysis revealed that the Not4 RRM-C affects a specific subset of Pol II-regulated genes, including those involved in transcription elongation, cyclin-dependent kinase regulated nutrient responses, and ribosomal biogenesis. The Not4 RING, RRM-C, or RING/RRM-C mutations cause a generalized increase in Pol II binding at a subset of these genes, yet their impact on gene expression does not always correlate with Pol II recruitment which suggests Not4 regulates their expression through additional mechanisms. Intriguingly, we find that while the Not4 RRM-C is dispensable for Ccr4-Not association with RNA Pol II, the Not4 RING domain is required for these interactions. Collectively, these data elucidate previously unknown roles for the conserved Not4 RRM-C and RING domains in regulating Ccr4-Not dependent functions in vivo.
登录
查看更多内容
影响因子：
4.8
作者：
Gulshan, Kailash;Thommandru, Bernice;Moye-Rowley, W. Scott
通讯作者：
Moye-Rowley, W. Scott
影响因子：
6.8
作者：
Daubner, Gerrit M.;Clery, Antoine;Allain, Frederic H-T
通讯作者：
Allain, Frederic H-T
DOI：
10.1007/978-3-319-46503-6_13
发表时间：
2017-01-01
期刊：
MACROMOLECULAR PROTEIN COMPLEXES: STRUCTURE AND FUNCTION
影响因子：
--
作者：
Collart, Martine A.;Panasenko, Olesya O.
通讯作者：
Panasenko, Olesya O.
影响因子：
4.8
作者：
Hanzawa, H;de Ruwe, MJ;Boelens, R
通讯作者：
Boelens, R
影响因子：
4.8
作者：
Babbarwal, Vinod;Fu, Jianhua;Reese, Joseph C.
通讯作者：
Reese, Joseph C.