Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT.
Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT.
复制标题
DOI：
10.1261/rna.066712.118
复制
发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Cheng C
中科院分区：
文献类型：
--
作者：
Harvey SE;Xu Y;Lin X;Gao XD;Qiu Y;Ahn J;Xiao X;Cheng C
上皮-间质转化（EMT）是一个基本的发育过程，在癌症转移中异常激活。在EMT期间，可变剪接发生动态变化。ESRP 1和hnRNPM分别是促进上皮剪接程序和间充质剪接程序的剪接调节剂。这些剪接因子在基因组尺度上的功能关系仍然难以捉摸。比较hnRNPM和ESRP 1的选择性剪接靶点，发现它们共同调节一组盒外显子事件，其中大多数显示不一致的剪接调节。由hnRNPM调节的不一致剪接事件显示出与EMT期间的剪接正相关;然而，一致事件没有，表明hnRNPM在EMT期间调节选择性剪接的作用比以前理解的更复杂。hnRNPM-ESRP 1共调节外显子附近的基序富集分析确定了hnRNPM抑制和ESRP 1增强外显子下游富含鸟嘌呤-尿苷的基序，支持竞争性结合这些顺式元件拮抗选择性剪接的一般模型。这组共调节外显子富含与细胞迁移和细胞骨架重组相关的基因，这些基因是与EMT相关的途径。共调节外显子的剪接水平与乳腺癌患者的生存率相关，并与EMT和乳腺癌亚型相关的基因集相关。这项研究确定了hnRNPM和ESRP 1在疾病相关背景下调节剪接的复杂相互作用模式。
The epithelial–mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they coregulate a set of cassette exon events, with the majority showing discordant splicing regulation. Discordant splicing events regulated by hnRNPM show a positive correlation with splicing during EMT; however, concordant events do not, indicating the role of hnRNPM in regulating alternative splicing during EMT is more complex than previously understood. Motif enrichment analysis near hnRNPM–ESRP1 coregulated exons identifies guanine–uridine rich motifs downstream from hnRNPM-repressed and ESRP1-enhanced exons, supporting a general model of competitive binding to these cis-elements to antagonize alternative splicing. The set of coregulated exons are enriched in genes associated with cell migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of coregulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtyping. This study identifies complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts.
登录
查看更多内容
替代RNA剪接和癌症。
影响因子：
7.3
作者：
Liu, Sali;Cheng, Chonghui
通讯作者：
Cheng, Chonghui
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
5.3
作者：
Dittmar, Kimberly A.;Jiang, Peng;Carstens, Russell P.
通讯作者：
Carstens, Russell P.
DOI：
10.1007/s12032-015-0593-z
发表时间：
2015-05
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Hernandez JR;Kim JJ;Verdone JE;Liu X;Torga G;Pienta KJ;Mooney SM
通讯作者：
Mooney SM
影响因子：
15.9
作者：
Brown, Rhonda L.;Reinke, Lauren M.;Cheng, Chonghui
通讯作者：
Cheng, Chonghui