HuR and GRSF1 Modulate the Nuclear Export and Mitochondrial Localization of the LncRNA RMRP

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2016 May 21

PMID 27198227

Citations 122

Authors

Ji Heon Noh

Kyoung Mi Kim

Kotb Abdelmohsen

Je-Hyun Yoon

Amaresh C Panda

Rachel Munk

Jiyoung Kim

Jessica Curtis

Christopher A Moad

Christina M Wohler

Fred E Indig

Wilson de Paula

Dawood B Dudekula

Supriyo De

Yulan Piao

Xiaoling Yang

Jennifer L Martindale

Rafael de Cabo

Myriam Gorospe

Affiliations

Soon will be listed here.

Abstract

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.

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