title: HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP.
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.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Noh
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Amaresh C
authors.initials: AC
authors.lastname: Panda
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Munk
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Curtis
authors.affiliation: Confocal Imaging Facility, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Moad
authors.affiliation: Confocal Imaging Facility, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wohler
authors.affiliation: Confocal Imaging Facility, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Fred E
authors.initials: FE
authors.lastname: Indig
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: de Paula
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Dawood B
authors.initials: DB
authors.lastname: Dudekula
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: D000067780:ELAV-Like Protein 1; C088356:GRSF1 protein, human; D039102:Poly(A)-Binding Proteins; C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: RNA-binding proteins; mitochondrial RNA import; nuclear RNA export; oxygen consumption rate; ribonucleoprotein complex