HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP

被引：180

作者：

Noh, Ji Heon ^{[1
]}

Kim, Kyoung Mi ^{[1
]}

Abdelmohsen, Kotb ^{[1
]}

Yoon, Je-Hyun ^{[1
]}

Panda, Amaresh C. ^{[1
]}

Munk, Rachel ^{[1
]}

Kim, Jiyoung ^{[1
]}

Curtis, Jessica ^{[2
]}

Moad, Christopher A. ^{[3
]}

Wohler, Christina M. ^{[3
]}

Indig, Fred E. ^{[3
]}

de Paula, Wilson ^{[1
]}

Dudekula, Dawood B. ^{[1
]}

De, Supriyo ^{[1
]}

Piao, Yulan ^{[1
]}

Yang, Xiaoling ^{[1
]}

Martindale, Jennifer L. ^{[1
]}

de Cabo, Rafael ^{[2
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA

[2] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA

[3] NIA, Confocal Imaging Facil, NIH, Baltimore, MD 21224 USA

来源：

GENES & DEVELOPMENT | 2016年 / 30卷 / 10期

基金：

美国国家卫生研究院;

关键词：

RNA-binding proteins; nuclear RNA export; ribonucleoprotein complex; mitochondrial RNA import; oxygen consumption rate; RNA-BINDING-PROTEIN; MESSENGER-RNA; RIBOSOMAL-RNA; POSTTRANSLATIONAL MODIFICATION; MRP; SEQUENCE; EXPRESSION; IMPORT; GENE; TRANSLATION;

D O I：

10.1101/gad.276022.115

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria are poorly characterized. Using affinity RNA pull-down followed by mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich RNA sequence-binding factor 1), that associated with the nuclear DNA-encoded lncRNA RMRP and mobilized it to mitochondria. In cultured human cells, HuR bound RMRP in the nucleus and mediated its CRM1 (chromosome region maintenance 1)-dependent export to the cytosol. After RMRP was imported into mitochondria, GRSF1 bound RMRP and increased its abundance in the matrix. Loss of GRSF1 lowered the mitochondrial levels of RMRP, in turn suppressing oxygen consumption rates and modestly reducing mitochondrial DNA replication priming. Our findings indicate that RBPs HuR and GRSF1 govern the cytoplasmic and mitochondrial localization of the lncRNA RMRP, which is encoded by nuclear DNA but has key functions in mitochondria.

引用

页码：1224 / 1239

页数：16

共 54 条

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