Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.
Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.
复制标题
DOI：
10.1016/j.cell.2009.06.016
复制
发表时间：
2009-08-21
期刊：
影响因子：
64.5
通讯作者：
Bartel DP
中科院分区：
文献类型：
--
作者：
Mayr C;Bartel DP
在癌细胞中，基因改变可以激活原癌基因，从而促进肿瘤发生。然而，癌基因的蛋白质产物有时过表达而原癌基因不改变。为了解释这一现象，我们发现，当与类似增殖的非转化细胞系相比时，癌细胞系通常表达大量3 ′非翻译区（UTR）较短的mRNA亚型。这些较短的异构体通常是由交替切割和多聚腺苷酸化（APA）产生的。APA具有功能性后果，较短的mRNA同种型表现出增加的稳定性，通常产生十倍以上的蛋白质，部分原因是由于microRNA介导的抑制作用的丧失。此外，原癌基因IGF2BP1/IMP-1的较短mRNA亚型的表达比全长注释mRNA的表达导致更多的致癌转化。APA在癌细胞中的高发病率，以及随之而来的3 ′ UTR抑制元件的丢失，表明APA在癌基因激活中的普遍作用，而没有遗传改变。
In cancer cells, genetic alterations can activate proto-oncogenes, thereby contributing to tumorigenesis. However, the protein products of oncogenes are sometimes over-expressed without alteration of the proto-oncogene. Helping to explain this phenomenon, we found that when compared to similarly proliferating non-transformed cell lines, cancer cell lines often expressed substantial amounts of mRNA isoforms with shorter 3′ untranslated regions (UTRs). These shorter isoforms usually resulted from alternative cleavage and polyadenylation (APA). The APA had functional consequences, with the shorter mRNA isoforms exhibiting increased stability and typically producing ten-fold more protein, in part through the loss of microRNA-mediated repression. Moreover, expression of the shorter mRNA isoform of the proto-oncogene IGF2BP1/IMP-1 led to far more oncogenic transformation than did expression of the full-length, annotated mRNA. The high incidence of APA in cancer cells, with consequent loss of 3′UTR repressive elements, suggests a pervasive role for APA in oncogene activation without genetic alteration.
登录
查看更多内容
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
11.5
作者：
Hoeflich, Klaus P.;O'Brien, Carol;Lackner, Mark R.
通讯作者：
Lackner, Mark R.
影响因子：
64.8
作者：
COLEMAN, MS;HUTTON, JJ;BOLLUM, FJ
通讯作者：
BOLLUM, FJ
DOI：
10.1073/pnas.0900028106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ji, Zhe;Lee, Ju Youn;Tian, Bin
通讯作者：
Tian, Bin
影响因子：
64.8
作者：
Amrani, Nadia;Ghosh, Shubhendu;Jacobson, Allan
通讯作者：
Jacobson, Allan