Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs.
Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs.
复制标题
人NOP2/NSUN1通过与盒子C/D snornps的非催化复合物形成来调节核糖体生物发生。
DOI：
10.1093/nar/gkac817
复制
发表时间：
2022-10-14
影响因子：
14.9
通讯作者：
Denicourt, Catherine
中科院分区：
文献类型：
--
作者：
Liao, Han;Gaur, Anushri;McConie, Hunter;Shekar, Amirtha;Wang, Karen;Chang, Jeffrey T.;Breton, Ghislain;Denicourt, Catherine
5-甲基胞嘧啶（m5C）是广泛存在于人类转录组中各种rna上的碱基修饰。在真核生物中，m5C由由7个人类成员组成的NSUN家族的酶（NSUN1-7）催化。在出芽酵母中，NOP2/NSUN1被认为是m5C沉积在25S核糖体RNA （rRNA）上所必需的核糖体生物发生因子。虽然已知人类NOP2/NSUN1在几种类型的癌症中是一个过表达的致癌基因，但其功能和底物的特征仍然很差。在这里，我们使用miCLIP-seq方法来鉴定人类NOP2/NSUN1 RNA底物。我们的分析表明，NOP2/NSUN1催化28S rRNA上4447位m5C的沉积。我们还发现NOP2/NSUN1结合到pre-rRNA转录物的5'ETS区域，并通过与盒C/D snoRNAs形成非催化复合物来调节pre-rRNA加工。我们提供的证据表明，NOP2/NSUN1促进了U3和U8 snorna募集到90s前核糖体颗粒上，并促进了它们稳定地组装成snoRNP复合物。值得注意的是，在低敲背景下，WT和催化失活的NOP2/NSUN1的表达都挽救了rRNA加工缺陷和box C/D snoRNP复合物的稳定组装，这表明NOP2/NSUN1介导的m5C在rRNA上的沉积不是核糖体合成所必需的。
5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m5C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5′ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m5C on rRNA is not required for ribosome synthesis.
登录
查看更多内容
影响因子：
7.3
作者：
Ciganda, Martin;Williams, Noreen
通讯作者：
Williams, Noreen
影响因子：
4.8
作者：
Dosil, M;Bustelo, XR
通讯作者：
Bustelo, XR
影响因子：
5.3
作者：
Dai, MS;Zeng, SX;Lu, H
通讯作者：
Lu, H
DOI：
10.1126/science.aau1646
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Frye M;Harada BT;Behm M;He C
通讯作者：
He C
影响因子：
14.9
作者：
Boccaletto P;Machnicka MA;Purta E;Piatkowski P;Baginski B;Wirecki TK;de Crécy-Lagard V;Ross R;Limbach PA;Kotter A;Helm M;Bujnicki JM
通讯作者：
Bujnicki JM