Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing.
Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing.
复制标题
DOI：
10.1016/j.molcel.2018.09.033
复制
发表时间：
2018-11-01
期刊：
影响因子：
16
通讯作者：
Ule J
中科院分区：
文献类型：
--
作者：
Blazquez L;Emmett W;Faraway R;Pineda JMB;Bajew S;Gohr A;Haberman N;Sibley CR;Bradley RK;Irimia M;Ule J
递归剪接 (RS) 首先定义一个“RS 外显子”，然后将其剪接到前面的外显子，从而创建递归 5' 剪接位点 (RS-5ss)。之前的研究主要集中在神秘的 RS 外显子上，现在我们发现外显子连接复合体 (EJC) 抑制数百个带注释的 RS 外显子，主要是组成型 RS 外显子。核心 EJC 因子以及外围因子 PNN 和 RNPS1 通过抑制 RS-5ss 上的剪接体组装来维持 RS 外显子包含。 EJC 还阻断位于外显子-外显子连接附近的 5ss，从而抑制隐秘微外显子的包含。带注释的 RS 外显子在后口动物中普遍存在，而神秘的 RS 外显子在果蝇中更为普遍，而 EJC 抑制 RS 的能力似乎较差。值得注意的是，RS 的不完全抑制也有助于几个人类 RS 外显子的生理选择性剪接。最后，小鼠中 EJC 因子 Magoh 的单倍体不足与大脑中 RS 外显子的跳跃有关，与小头畸形表型和人类疾病相关。人类 mRNA 中的数百个 RS 外显子在外显子-外显子连接处重建神秘的 5ss EJC 抑制 RS 外显子的递归剪接以保持转录组完整性 RS 有助于生理选择性剪接 EJC 介导的抑制在后口动物和大脑中特别重要 Blazquez 等人。证明可以通过一种称为递归剪接的机制从部分剪接的转录本中跳过数百个带注释的外显子。外显子连接复合物的沉积会抑制这种机制，这在后口动物和大脑中尤其重要，它可能导致小头畸形表型和人类疾病。
Recursive splicing (RS) starts by defining an “RS-exon,” which is then spliced to the preceding exon, thus creating a recursive 5′ splice site (RS-5ss). Previous studies focused on cryptic RS-exons, and now we find that the exon junction complex (EJC) represses RS of hundreds of annotated, mainly constitutive RS-exons. The core EJC factors, and the peripheral factors PNN and RNPS1, maintain RS-exon inclusion by repressing spliceosomal assembly on RS-5ss. The EJC also blocks 5ss located near exon-exon junctions, thus repressing inclusion of cryptic microexons. The prevalence of annotated RS-exons is high in deuterostomes, while the cryptic RS-exons are more prevalent in Drosophila, where EJC appears less capable of repressing RS. Notably, incomplete repression of RS also contributes to physiological alternative splicing of several human RS-exons. Finally, haploinsufficiency of the EJC factor Magoh in mice is associated with skipping of RS-exons in the brain, with relevance to the microcephaly phenotype and human diseases. Hundreds of RS-exons in human mRNAs reconstitute cryptic 5ss at exon-exon junctions EJC represses recursive splicing of RS-exons to preserve transcriptome integrity RS contributes to physiological alternative splicing EJC-mediated repression is particularly important in deuterostomes and in the brain Blazquez et al. demonstrate that hundreds of annotated exons can be skipped from partly spliced transcripts through a mechanism called recursive splicing. Deposition of the exon junction complex represses this mechanism, which is particularly relevant in deuterostomes and the brain, where it can contribute to a microcephaly phenotype and human disease.
登录
查看更多内容
影响因子：
4.8
作者：
Huppertz, Ina;Attig, Jan;D'Ambrogio, Andrea;Easton, Laura E.;Sibley, Christopher R.;Sugimoto, Yoichiro;Tajnik, Mojca;Koenig, Julian;Ule, Jernej
通讯作者：
Ule, Jernej
影响因子：
16.8
作者：
Ballut, L;Marchadier, B;Le Hir, H
通讯作者：
Le Hir, H
影响因子：
16.8
作者：
Murachelli, Andrea Giovanni;Ebert, Judith;Conti, Elena
通讯作者：
Conti, Elena
影响因子：
3.7
作者：
Aerne BL;Gailite I;Sims D;Tapon N
通讯作者：
Tapon N
影响因子：
64.5
作者：
Ashton-Beaucage, Dariel;Udell, Christian M.;Therrien, Marc
通讯作者：
Therrien, Marc