Mammalian mitochondrial RNAs are degraded in the mitochondrial intermembrane space by RNASET2
Peipei Liu, Jinliang Huang, Qian Zheng, Leiming Xie, Xinping Lu, Jie Jin, Geng Wang
Mammalian mitochondrial RNAs are degraded in the mitochondrial intermembrane space by RNASET2
Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMSlocalized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.
mitochondria / intermembrane space / ribonuclease / mtRNA / RNA degradation / decay / RNASET2 / RNase T2 / inner membrane / transport / RNA trafficking
[1] |
AcquatiF, BertilaccioS, GrimaldiA, MontiL, CinquettiR, BonettiP, LualdiM, VidalinoL, FabbriM, SaccoMG
CrossRef
Google scholar
|
[2] |
AlfonzoJD, ThiemannOH, SimpsonL (1998) Purification and characterization of MAR1. A mitochondrial associated ribonuclease from Leishmania tarentolae.J Biol Chem273:30003–30011
CrossRef
Google scholar
|
[3] |
AndersonS, BankierAT, BarrellBG, de BruijnMH, CoulsonAR, DrouinJ, EperonIC, NierlichDP, RoeBA, SangerF
CrossRef
Google scholar
|
[4] |
Bienertova-VaskuJ, SanaJ, SlabyO (2013) The role of microRNAs in mitochondria in cancer.Cancer Lett336:1–7
CrossRef
Google scholar
|
[5] |
BonawitzND, RodehefferMS, ShadelGS (2006) Defective mitochondrial gene expression results in reactive oxygen speciesmediated inhibition of respiration and reduction of yeast life span.Mol Cell Biol26:4818–4829
CrossRef
Google scholar
|
[6] |
BorowskiLS, DziembowskiA, HejnowiczMS, StepienPP, SzczesnyRJ (2013) Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci.Nucleic Acids Res41:1223–1240
CrossRef
Google scholar
|
[7] |
BruniF, GramegnaP, OliveiraJM, LightowlersRN, Chrzanowska-LightowlersZM (2013) REXO2 is an oligoribonuclease active in human mitochondria.PLoS ONE8:e64670
CrossRef
Google scholar
|
[8] |
ChangDD, ClaytonDA (1989) Mouse RNAase MRP RNA is encoded by a nuclear gene and contains a decamer sequence complementary to a conserved region of mitochondrial RNA substrate.Cell56:131–139
CrossRef
Google scholar
|
[9] |
ChenHW, RaineyRN, BalatoniCE, DawsonDW, TrokeJJ, WasiakS, HongJS, McBrideHM, KoehlerCM, TeitellMA
CrossRef
Google scholar
|
[10] |
ChujoT, OhiraT, SakaguchiY, GoshimaN, NomuraN, NagaoA, SuzukiT (2012) LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria.Nucleic Acids Res40:8033–8047
CrossRef
Google scholar
|
[11] |
ClementeP, PajakA, LaineI, WibomR,WedellA,FreyerC,WredenbergA (2015) SUV3 helicase is required for correct processing of mitochondrial transcripts.Nucleic Acids Res43:7398–7413
CrossRef
Google scholar
|
[12] |
CoteJ, Ruiz-CarrilloA (1993) Primers for mitochondrial DNA replication generated by endonuclease G.Science261:765–769
CrossRef
Google scholar
|
[13] |
DaoudR, ForgetL, LangBF (2012) Yeast mitochondrial RNase P, RNase Z and the RNA degradosome are part of a stable supercomplex.Nucleic Acids Res40:1728–1736
CrossRef
Google scholar
|
[14] |
DuarteFV, PalmeiraCM, RoloAP (2015) The emerging role of MitomiRs in the pathophysiology of human disease.Adv Exp Med Biol888:123–154
CrossRef
Google scholar
|
[15] |
DucheneAM, PujolC, Marechal-DrouardL (2009) Import of tRNAs and aminoacyl-tRNA synthetases into mitochondria.Curr Genet55:1–18
CrossRef
Google scholar
|
[16] |
DziembowskiA, MalewiczM, MinczukM, GolikP, DmochowskaA, StepienPP (1998) The yeast nuclear gene DSS1, which codes for a putative RNase II, is necessary for the function of the mitochondrial degradosome in processing and turnover of RNA.Mol Gen Genet260:108–114
CrossRef
Google scholar
|
[17] |
HallbergBM, LarssonNG (2014) Making proteins in the powerhouse.Cell Metab20:226–240
CrossRef
Google scholar
|
[18] |
HanS, UdeshiND, DeerinckTJ, SvinkinaT, EllismanMH, CarrSA, TingAY (2017) Proximity biotinylation as a method for mapping proteins associated with mtDNA in living cells.Cell Chem Biol24:404–414
CrossRef
Google scholar
|
[19] |
HennekeM, DiekmannS, OhlenbuschA, KaiserJ, EngelbrechtV, KohlschutterA, KratznerR, Madruga-GarridoM, MayerM, OpitzL
CrossRef
Google scholar
|
[20] |
IrieM (1999) Structure-function relationships of acid ribonucleases: lysosomal, vacuolar, and periplasmic enzymes.Pharmacol Ther81:77–89
CrossRef
Google scholar
|
[21] |
JanCH, WilliamsCC, WeissmanJS (2014) Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling.Science346:1257521
CrossRef
Google scholar
|
[22] |
KhidrL,WuG,DavilaA, ProcaccioV, WallaceD, LeeWH (2008) Role of SUV3 helicase in maintaining mitochondrial homeostasis in human cells.J Biol Chem283:27064–27073
CrossRef
Google scholar
|
[23] |
KimDI, RouxKJ (2016) Filling the void: proximity-based labeling of proteins in living cells.Trends Cell Biol26:804–817
CrossRef
Google scholar
|
[24] |
LevyS, AllerstonCK, LiveanuV, HabibMR, GileadiO, SchusterG (2016) Identification of LACTB2, a metallo-beta-lactamase protein, as a human mitochondrial endoribonuclease.Nucleic Acids Res44:1813–1832
CrossRef
Google scholar
|
[25] |
LuhtalaN, ParkerR (2010) T2 Family ribonucleases: ancient enzymes with diverse roles.Trends Biochem Sci35:253–259
CrossRef
Google scholar
|
[26] |
MaleckiM, StepienPP, GolikP (2010) Assays of the helicase, ATPase, and exoribonuclease activities of the yeast mitochondrial degradosome.Methods Mol Biol587:339–358
CrossRef
Google scholar
|
[27] |
MargossianSP, LiH, ZassenhausHP, ButowRA (1996) The DExH box protein Suv3p is a component of a yeast mitochondrial 3’-to-5’ exoribonuclease that suppresses group I intron toxicity.Cell84:199–209
CrossRef
Google scholar
|
[28] |
MercerTR, NephS, DingerME, CrawfordJ, SmithMA, ShearwoodAM, HaugenE, BrackenCP, RackhamO, StamatoyannopoulosJA
CrossRef
Google scholar
|
[29] |
MiczakA, KaberdinVR, WeiCL, Lin-ChaoS (1996) Proteins associated with RNase E in a multicomponent ribonucleolytic complex.Proc Natl Acad Sci USA93:3865–3869
CrossRef
Google scholar
|
[30] |
MishraP, ChanDC (2016) Metabolic regulation of mitochondrial dynamics.J Cell Biol212:379–387
CrossRef
Google scholar
|
[31] |
Nesiel-NuttmanL, DoronS, SchwartzB, ShoseyovO (2015) Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization.Oncoscience2:31–43
CrossRef
Google scholar
|
[32] |
NohJH, KimKM, AbdelmohsenK, YoonJH, PandaAC, MunkR, KimJ, CurtisJ, MoadCA, WohlerCM
|
[33] |
OhsatoT, IshiharaN, MutaT, UmedaS, IkedaS, MiharaK, HamasakiN, KangD (2002) Mammalian mitochondrial endonuclease G. Digestion of R-loops and localization in intermembrane space.Eur J Biochem FEBS269:5765–5770
CrossRef
Google scholar
|
[34] |
PortnoyV, PalnizkyG, Yehudai-ResheffS, GlaserF, SchusterG (2008) Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences in RNA binding and response to phosphate compared to its bacterial and chloroplast counterparts.RNA14:297–309
CrossRef
Google scholar
|
[35] |
RouxKJ, KimDI, RaidaM, BurkeB (2012) A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells.J Cell Biol196:801–810
CrossRef
Google scholar
|
[36] |
RubioMA, RinehartJJ, KrettB, Duvezin-CaubetS, ReichertAS, SollD, AlfonzoJD (2008) Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import.Proc Natl Acad Sci USA105:9186–9191
CrossRef
Google scholar
|
[37] |
SanchezMI, MercerTR, DaviesSM, ShearwoodAM, NygardKK, RichmanTR, MattickJS, RackhamO, FilipovskaA (2011) RNA processing in human mitochondria.Cell Cycle10:2904–2916
CrossRef
Google scholar
|
[38] |
SarkarD, ParkES, EmdadL, RandolphA, ValerieK, FisherPB (2005) Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence.Mol Cell Biol25:7333–7343
CrossRef
Google scholar
|
[39] |
SatoR, Arai-IchinoiN, KikuchiA, MatsuhashiT, Numata-UematsuY, UematsuM, FujiiY, MurayamaK, OhtakeA, AbeT
CrossRef
Google scholar
|
[40] |
SchaferB, HansenM, LangBF (2005) Transcription and RNAprocessing in fission yeast mitochondria.RNA11:785–795
CrossRef
Google scholar
|
[41] |
SimpsonAM, BakalaraN, SimpsonL (1992) A ribonuclease activity is activated by heparin or by digestion with proteinase K in mitochondrial extracts of Leishmania tarentolae.J Biol Chem267:6782–6788
|
[42] |
SlomovicS, PortnoyV, Yehudai-ResheffS, BronshteinE, SchusterG (2008) Polynucleotide phosphorylase and the archaeal exosome as poly(A)-polymerases.Biochim et Biophys Acta1779:247–255
CrossRef
Google scholar
|
[43] |
SlomovicS, SchusterG (2008) Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA.RNA14:310–323
CrossRef
Google scholar
|
[44] |
SmirnovA, EntelisN, MartinRP, TarassovI (2011) Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18.Genes Dev25:1289–1305
CrossRef
Google scholar
|
[45] |
SzczesnyRJ, BorowskiLS, MaleckiM, WojcikMA, StepienPP, GolikP (2012) RNA degradation in yeast and human mitochondria.Biochim et Biophys Acta1819:1027–1034
CrossRef
Google scholar
|
[46] |
SzczesnyRJ, WojcikMA, BorowskiLS, SzewczykMJ, SkrokMM, GolikP, StepienPP (2013) Yeast and human mitochondrial helicases.Biochim et Biophys Acta1829:842–853
CrossRef
Google scholar
|
[47] |
VedrenneV, GowherA, De LonlayP, NitschkeP, SerreV, BoddaertN, AltuzarraC, Mager-HeckelAM, ChretienF, EntelisN
CrossRef
Google scholar
|
[48] |
von AmelnS, WangG, BoulouizR, RutherfordMA, SmithGM, LiY, PogodaHM, NurnbergG, StillerB, VolkAE
CrossRef
Google scholar
|
[49] |
WangG, ChenHW, OktayY, ZhangJ, AllenEL, SmithGM, FanKC, HongJS, FrenchSW, McCafferyJM
CrossRef
Google scholar
|
[50] |
WilliamsCC, JanCH, WeissmanJS (2014) Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling.Science346:748–751
CrossRef
Google scholar
|
[51] |
ZhangX, ZuoX, YangB, LiZ, XueY, ZhouY, HuangJ, ZhaoX, ZhouJ, YanY
CrossRef
Google scholar
|
[52] |
ZhouQ, LiH, LiH, NakagawaA, LinJL, LeeES, HarryBL, Skeen-GaarRR, SuehiroY, WilliamD
CrossRef
Google scholar
|
/
〈 | 〉 |