HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP
- Ji Heon Noh1,4,
- Kyoung Mi Kim1,4,
- Kotb Abdelmohsen1,
- Je-Hyun Yoon1,
- Amaresh C. Panda1,
- Rachel Munk1,
- Jiyoung Kim1,
- Jessica Curtis2,
- Christopher A. Moad3,
- Christina M. Wohler3,
- Fred E. Indig3,
- Wilson de Paula1,
- Dawood B. Dudekula1,
- Supriyo De1,
- Yulan Piao1,
- Xiaoling Yang1,
- Jennifer L. Martindale1,
- Rafael de Cabo2 and
- Myriam Gorospe1
- 1Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
- 2Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
- 3Confocal Imaging Facility, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
- Corresponding author: myriam-gorospe{at}nih.gov
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↵4 These authors contributed equally to this work.
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.
Keywords
- RNA-binding proteins
- nuclear RNA export
- ribonucleoprotein complex
- mitochondrial RNA import
- oxygen consumption rate
Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.276022.115.
- Received December 6, 2015.
- Accepted April 14, 2016.
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