HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP.
HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP.
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DOI：
10.1101/gad.276022.115
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发表时间：
2016-05-15
影响因子：
10.5
通讯作者：
Gorospe M
中科院分区：
文献类型：
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作者：
Noh JH;Kim KM;Abdelmohsen K;Yoon JH;Panda AC;Munk R;Kim J;Curtis J;Moad CA;Wohler CM;Indig FE;de Paula W;Dudekula DB;De S;Piao Y;Yang X;Martindale JL;de Cabo R;Gorospe M
Noh等人发现了两种RNA结合蛋白（RBP）-HuR和GRSF 1-与核DNA编码的lncRNA RMRP相关，并将其动员到线粒体。在培养的人类细胞中，HuR在细胞核中结合RMRP，并介导其CRM 1依赖性出口到胞质溶胶。RMRP进入线粒体后，GRSF 1结合RMRP并增加其在基质中的丰度。一些线粒体长链非编码RNA（lncRNA）由核DNA编码，但介导其转运至线粒体的机制尚不清楚。使用亲和RNA下拉，然后质谱分析，我们发现了两个RNA结合蛋白（RBP），HuR（人抗原R）和GRSF 1（富含G的RNA序列结合因子1），与核DNA编码的lncRNA RMRP相关，并将其动员到线粒体。在培养的人类细胞中，HuR在细胞核中结合RMRP，并介导其CRM 1（染色体区域维持1）依赖性出口到胞质溶胶。RMRP进入线粒体后，GRSF 1结合RMRP并增加其在基质中的丰度。GRSF 1的缺失降低了RMRP的线粒体水平，进而抑制了氧消耗速率并适度减少了线粒体DNA复制启动。我们的研究结果表明，RBPs HuR和GRSF 1支配lncRNA RMRP的细胞质和线粒体定位，lncRNA RMRP由核DNA编码，但在线粒体中具有关键功能。
Noh et al. found two RNA-binding proteins (RBPs)—HuR and GRSF1—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-dependent export to the cytosol. After RMRP was imported into mitochondria, GRSF1 bound RMRP and increased its abundance in the matrix. 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.