HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA <i>RMRP</i>

Noh, Ji Heon; Kim, Kyoung Mi; Abdelmohsen, Kotb; Yoon, Je‐Hyun; Panda, Amaresh C.; Munk, Rachel; Kim, Jiyoung; Curtis, Jessica; Moad, Christopher A.; Wöhler, Christina; Indig, Fred E.; Paula, Wilson de; Dudekula, Dawood B.; De, Supriyo; Piao, Yulan; Yang, Xiaoling; Martindale, Jennifer L.; Cabo, Rafael de; Gorospe, Myriam

doi:10.1101/gad.276022.115

Cited by 181 publications

(162 citation statements)

References 57 publications

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“…One such lncRNA is the RNA component of the RNA processing endoribonuclease (RMRP) that is transported by RNA-binding proteins human antigen R, G-rich RNA sequence binding factor 1, and polynucleotide phosphorylase (PNPase) in the mitochondria, where it participates in mtDNA replication and transcription. Lowering the RMRP levels led to a reduction in the basal oxygen consumption rate as well as levels of the ATP6, COX1, and CYTB proteins (Wang et al, 2010;Noh et al, 2016).…”

Section: Long Noncoding Rnasmentioning

confidence: 98%

“…Lowering the RMRP levels led to a reduction in the basal oxygen consumption rate as well as levels of the ATP6, COX1, and CYTB proteins (Wang et al, 2010;Noh et al, 2016). One such lncRNA is the RNA component of the RNA processing endoribonuclease (RMRP) that is transported by RNA-binding proteins human antigen R, G-rich RNA sequence binding factor 1, and polynucleotide phosphorylase (PNPase) in the mitochondria, where it participates in mtDNA replication and transcription.…”

Section: Long Noncoding Rnasmentioning

confidence: 99%

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Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

105

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Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded within mtDNA, the mitochondrial proteome comprises over 1500 proteins that are encoded by nuclear genes and translocated to the mitochondria for the purpose of maintaining mitochondrial function. Regulation of mtDNA and mitochondrial proteins by epigenetic changes and post‐translational modifications facilitate crosstalk between the nucleus and the mitochondria and ultimately lead to the maintenance of cellular health and homeostasis. DNA methyl transferases have been identified in the mitochondria implicating that methylation occurs within this organelle; however, the extent to which mtDNA is methylated has been debated for many years. Mechanisms of demethylation within this organelle have also been postulated, but the exact mechanisms and their outcomes is still an active area of research. Mitochondrial dysfunction in the form of altered gene expression and ATP production, resulting from epigenetic changes, can lead to various conditions including aging‐related neurodegenerative disorders, altered metabolism, changes in circadian rhythm, and cancer. Here, we provide an overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones). We also highlight the influence of xenobiotics such as airborne environmental pollutants, contamination from heavy metals, and therapeutic drugs on mtDNA methylation. Environ. Mol. Mutagen., 60:668–682, 2019. © 2019 Wiley Periodicals, Inc.

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Section: Long Noncoding Rnasmentioning

confidence: 98%

Section: Long Noncoding Rnasmentioning

confidence: 99%

Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

105

View full text Add to dashboard Cite

show abstract

“…In another recent study, Noh et al () reported two RBPs that contributed to the subcellular mobilization of the organelle‐specific localization of lncRNP complexes. A lncRNA abundant in the nucleus, RMRP (an RNA component of the mitochondrial RNA‐processing endoribonuclease) associated with the RBP HuR in the nucleus, and the resulting lncRNP was mobilized into the cytoplasm through CRM1 (chromosome region maintenance 1)‐dependent nuclear export.…”

Section: Subcellular Mobilization Of Lncrnasmentioning

confidence: 99%

Cytoplasmic functions of long noncoding RNAs

et al. 2018

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Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions. Here, we review our current knowledge of cytoplasmic lncRNAs and the different levels of gene regulation controlled by cytoplasmic lncRNA complexes, including mRNA turnover, translation, protein stability, sponging of cytosolic factors, and modulation of signaling pathways. We conclude by discussing areas of future study needed to elucidate comprehensively the biology of lncRNAs, to further understand the impact of lncRNAs on physiology and design lncRNA-centered therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

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“…It was found to associate with the microRNA let-7, 6,7 although the consequences of this interaction are unclear, and with several long noncoding (lnc)RNAs, including LINCRNAP21, HOTAIR, and RMRP, influencing their stability or subcellular localization. 6,8,9 However, whether or not HuR binds to circular RNAs (circRNAs) and the functional consequences of these interactions have not been studied. Circular RNAs had been observed for several decades, but their high abundance and function have only begun to be appreciated with the advent of new sequencing and molecular biology techniques.…”

Section: Introductionmentioning

confidence: 99%

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

et al. 2017

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HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analysis revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA. Evaluation of PABPN1 mRNA polysomes indicated that PABPN1 translation was modulated positively by HuR and hence negatively by CircPABPN1. We propose that the extensive binding of CircPABPN1 to HuR prevents HuR binding to PABPN1 mRNA and lowers PABPN1 translation, providing the first example of competition between a circRNA and its cognate mRNA for an RBP that affects translation.

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

Cited by 181 publications

References 57 publications

Mitochondrial DNA: Epigenetics and environment

Mitochondrial DNA: Epigenetics and environment

Cytoplasmic functions of long noncoding RNAs

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

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