A Mitochondria-to-nucleus Regulation Mediated by the Nuclear-translocated Mitochondrial LncRNAs

Overview

Journal PLoS Genet

Date 2025 Jan 27

PMID 39869642

Authors

Jia Li

Ruoling Bai

Yulian Zhou

Xu Song

Ling Li

Affiliations

Soon will be listed here.

Abstract

A bidirectional nucleus-mitochondria communication is essential for homeostasis and stress. By acting as critical molecules, the nuclear-encoded lncRNAs (nulncRNAs) have been implicated in the nucleus-to-mitochondria anterograde regulation. However, role of mitochondrial-derived lncRNAs (mtlncRNAs) in the mitochondria-to-nucleus retrograde regulation remains elusive. Here, we identify functional implication of the mtlncRNAs MDL1AS, lncND5 and lncCyt b in retrograde regulation. Mediated by HuR and PNPT1 proteins, the mtlncRNAs undergo a mitochondria-to-nucleus traveling and then regulate a network of nuclear genes. Moreover, as an example of the functional consequence, we showed that the nuclear-translocated lncCyt b cooperates with the splicing factor hnRNPA2B1 to influence several aspects of cell metabolism including glycolysis, possibly through their regulatory effect on the post-transcriptional processing of related nuclear genes. This study advances our knowledge in mitochondrial biology and provides new insights into the role of mtlncRNAs in mitochondria-nucleus communications.

Citing Articles

Allosteric genetically encoded biosensor for spatiotemporal monitoring of endogenous RNA dynamics in living cells.

Yuan D, He H, Song W, Ma D, Xie M, Wang Y Proc Natl Acad Sci U S A. 2025; 122(7):e2409309122.

PMID: 39933002 PMC: 11848333. DOI: 10.1073/pnas.2409309122.

References

Cheng Y, Liu P, Zheng Q, Gao G, Yuan J, Wang P . Mitochondrial Trafficking and Processing of Telomerase RNA TERC. Cell Rep. 2018; 24(10):2589-2595. DOI: 10.1016/j.celrep.2018.08.003. View

Tomecki R, Dmochowska A, Gewartowski K, Dziembowski A, Stepien P . Identification of a novel human nuclear-encoded mitochondrial poly(A) polymerase. Nucleic Acids Res. 2004; 32(20):6001-14. PMC: 534615. DOI: 10.1093/nar/gkh923. View

Brennan C, Steitz J . HuR and mRNA stability. Cell Mol Life Sci. 2001; 58(2):266-77. PMC: 11146503. DOI: 10.1007/PL00000854. View

Mottis A, Herzig S, Auwerx J . Mitocellular communication: Shaping health and disease. Science. 2019; 366(6467):827-832. DOI: 10.1126/science.aax3768. View

Lane N, Martin W . The energetics of genome complexity. Nature. 2010; 467(7318):929-34. DOI: 10.1038/nature09486. View

Noh J, Kim K, Abdelmohsen K, Yoon J, Panda A, Munk R . HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev. 2016; 30(10):1224-39. PMC: 4888842. DOI: 10.1101/gad.276022.115. View

Gao S, Tian X, Chang H, Sun Y, Wu Z, Cheng Z . Two novel lncRNAs discovered in human mitochondrial DNA using PacBio full-length transcriptome data. Mitochondrion. 2017; 38:41-47. DOI: 10.1016/j.mito.2017.08.002. View

Wu M, Tong C, Yan W, To K, Cho W . The RNA Binding Protein HuR: A Promising Drug Target for Anticancer Therapy. Curr Cancer Drug Targets. 2018; 19(5):382-399. DOI: 10.2174/1568009618666181031145953. View

Cannon M, Irwin M, Pinkert C . Mitochondrially-imported RNA in drug discovery. Drug Dev Res. 2015; 76(2):61-71. DOI: 10.1002/ddr.21241. View

10.

Huang J, Wu S, Wang P, Wang G . Non-coding RNA Regulated Cross-Talk Between Mitochondria and Other Cellular Compartments. Front Cell Dev Biol. 2021; 9:688523. PMC: 8369480. DOI: 10.3389/fcell.2021.688523. View

11.

Liu X, Wang X, Li J, Hu S, Deng Y, Yin H . Identification of mecciRNAs and their roles in the mitochondrial entry of proteins. Sci China Life Sci. 2020; 63(10):1429-1449. DOI: 10.1007/s11427-020-1631-9. View

12.

Gusic M, Prokisch H . ncRNAs: New Players in Mitochondrial Health and Disease?. Front Genet. 2020; 11:95. PMC: 7059738. DOI: 10.3389/fgene.2020.00095. View

13.

Wang K, Long B, Zhou L, Liu F, Zhou Q, Liu C . CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun. 2014; 5:3596. DOI: 10.1038/ncomms4596. View

14.

Chen H, Rainey R, Balatoni C, Dawson D, Troke J, Wasiak S . Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis. Mol Cell Biol. 2006; 26(22):8475-87. PMC: 1636764. DOI: 10.1128/MCB.01002-06. View

15.

Schmidt O, Pfanner N, Meisinger C . Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol. 2010; 11(9):655-67. DOI: 10.1038/nrm2959. View

16.

Quiros P, Mottis A, Auwerx J . Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol. 2016; 17(4):213-26. DOI: 10.1038/nrm.2016.23. View

17.

Prechtel A, Chemnitz J, Schirmer S, Ehlers C, Langbein-Detsch I, Stulke J . Expression of CD83 is regulated by HuR via a novel cis-active coding region RNA element. J Biol Chem. 2006; 281(16):10912-25. DOI: 10.1074/jbc.M510306200. View

18.

Peng S, Chen C, Xu N, Shyu A . RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein. EMBO J. 1998; 17(12):3461-70. PMC: 1170682. DOI: 10.1093/emboj/17.12.3461. View

19.

Spinelli J, Haigis M . The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018; 20(7):745-754. PMC: 6541229. DOI: 10.1038/s41556-018-0124-1. View

20.

Fuke H, Ohno M . Role of poly (A) tail as an identity element for mRNA nuclear export. Nucleic Acids Res. 2007; 36(3):1037-49. PMC: 2241894. DOI: 10.1093/nar/gkm1120. View