MicroRNA-mediated mRNA Translation Activation in Quiescent Cells and Oocytes Involves Recruitment of a Nuclear microRNP

被引：114

作者：

Truesdell, S. S. ^{[1
]}

Mortensen, R. D. ^{[1
]}

Seo, M. ^{[1
]}

Schroeder, J. C. ^{[1
]}

Lee, J. H. ^{[1
]}

LeTonqueze, O. ^{[1
]}

Vasudevan, S. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

关键词：

PROTEIN; REPRESSION; CYCLE; GW182; EXPRESSION; MIRNAS; LOCALIZATION; BIOGENESIS; COMPONENT; CCR4-NOT;

D O I：

10.1038/srep00842

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MicroRNAs can promote translation of specific mRNAs in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes. We report that microRNA-mediated upregulation of target mRNAs in oocytes is dependent on nuclear entry of the microRNA; cytoplasmically-injected microRNA repress target mRNAs. Components of the activation microRNP, AGO, FXR1 (FXR1-iso-a) and miR16 are present in the nucleus and cytoplasm. Importantly, microRNA target mRNAs for upregulation, Myt1, TNF alpha and a reporter bearing the TNF alpha AU-rich, microRNA target sequence, are associated with AGO in immature oocyte nuclei and AGO2 in G0 human nuclei, respectively. mRNAs that are repressed or lack target sites are not associated with nuclear AGO. Crosslinking-coupled immunopurification revealed greater association of AGO2 with FXR1 in the nucleus compared to cytoplasm. Consistently, overexpression of FXR1-iso-a rescues activation of cytoplasmically-injected RNAs and in low density, proliferating cells. These data indicate the importance of a compartmentalized AGO2-FXR1-iso-a complex for selective recruitment for microRNA-mediated upregulation.

引用

页数：12