Human SUV3 helicase in the cell nucleus regulates the growth rate of HeLa cells.
AbstractThe human SUV3 helicase (hSuv3p, hSUV3, SUPV3L1) is a DNA/RNA unwinding enzyme belonging to the class of DexH-box helicases. It localizes predominantly in mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome with exonuclease PNP (polynucleotide phosphorylase). Association of this complex with polyA polymerase modulates mitochondrial polyA tails. Silencing of the SUV3 gene was shown to inhibit the cell cycle and to induce apoptosis in human cell lines. However, since small amounts of the SUV3 helicase were found in cell nuclei, it was not clear whether the observed phenotypes of SUV3 depletion were of mitochondrial or nuclear origin. In order to answer this question we designed gene constructs able to inhibit SUV3 nuclear activity exclusively. The results indicate that the observed growth rate impairment upon SUV3 depletion is due to its nuclear function(s). Unexpectedly, overexpression of the nuclear-targeted wild-type copies of SUV3 gene resulted in higher growth rate. Our results indicate that the nucleus-associated human SUV3 protein is an important factor in regulation of the cell cycle.
Borowski LS, Dziembowski A, Hejnowicz MS, Stepien PP, Szczesny RJ (2013) Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci. Nucleic Acids Res. 41: 1223-40. DOI: 10.1093/nar/gks1130
Chen PL, Chen CF, Chen Y, Guo XE, Huang CK, Shew JY, Reddick RL, Wallace DC, Lee WH (2013) Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan. Oncogene 32: 1193-201. DOI: 10.1038/onc.2012.120.
Dmochowska A, Kalita K, Krawczyk M, Golik P, Mroczek K, Lazowska J, Stepień PP, Bartnik E. (1999) A human putative Suv3-like RNA helicase is conserved between Rhodobacter and all eukaryotes. Acta Biochim Pol. 46: 155-62.
Dziembowski A, Piwowarski J, Hoser R, Minczuk M, Dmochowska A, Siep M, van derSpek H, Grivell L, Stepien PP (2003) The yeast mitochondrial degradosome. Its composition,interplay between RNA helicase and RNase activities and the role in mitochondrial RNA metabolism. J Biol Chem. 278: 1603-1611. DOI: 10.1074/jbc.M208287200
Irelan JT, Wu MJ, Morgan J, Ke N, Xi B, Wang X, Xu X, Abassi YA (2011) Rapid and quantitative assessment of cell quality, identity, and functionality for cell-based assays using real-time cellular analysis. J Biomol Screen. 16: 313-22. DOI: 10.1177/1087057110397359
Margossian SP, Li H, Zassenhaus HP, Butow RA (1996) The DExH box protein Suv3p is a component of a yeast mitochondrial 3'-to-5' exoribonuclease that suppresses group I intron toxicity. Cell. 84: 199-209.
Minczuk M, Piwowarski J, Papworth MA, Awiszus K, Schalinski S, Dziembowski A, Dmochowska A, Bartnik E, Tokatlidis K, Stepien PP, Borowski P (2002) Localisation of the human hSuv3p helicase in the mitochondrial matrix and its preferential unwinding of dsDNA. Nucleic Acids Res. 30: 5074-86.
Paul E, Cronan R, Weston PJ, Boekelheide K, Sedivy JM, Lee SY, Wiest DL, Resnick MB, Klysik JE (2009) Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality. Mamm Genome. 20: 92-108. DOI: 10.1007/s00335-008-9168-z
Pereira M, Mason P, Szczesny RJ, Maddukuri L, Dziwura S, Jedrzejczak R, Paul E, Wojcik A, Dybczynska L, Tudek B, Bartnik E, Klysik J, Bohr VA, Stepien PP (2007) Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality. Mech Ageing Dev. 128: 609-17. DOI: 10.1016/j.mad.2007.09.001
Rogowska AT, Puchta O, Czarnecka AM, Kaniak A, Stepien PP, Golik P (2006) Balance between transcription and RNA degradation is vital for Saccharomyces cerevisiae mitochondria: reduced transcription rescues the phenotype of deficient RNA degradation. Mol Biol Cell. 17: 1184-93. DOI: 10.1091/mbc.E05-08-0796
Sahoo RK, Ansari MW, Tuteja R, Tuteja N (2014) OsSUV3 transgenic rice maintains higher endogenous levels of plant hormones that mitigates adverse effects of salinity and sustains crop productivity. Rice (N Y). 7: 17. DOI: 10.1186/s12284-014-0017-2
Sahoo RK, Ansari MW, Tuteja R, Tuteja N (2015) Salt tolerant SUV3 overexpressing transgenic rice plants conserve physicochemical properties and microbial communities of rhizosphere. Chemosphere. 119: 1040-7. DOI: 10.1016/j.chemosphere.2014.08.011.
Shu Z, Vijayakumar S, Chen CF, Chen PL, Lee WH (2004) Purified human SUV3p exhibits multiple-substrate unwinding activity upon conformational change. Biochemistry. 43: 4781-4790. DOI: 10.1021/bi0356449
Stepien PP, Margossian SP, Landsman D, Butow RA (1992) The yeast nuclear gene suv3 affecting mitochondrial post-transcriptional processes encodes a putative ATP-dependent RNA helicase. Proc. Natl. Acad. Sci. 89: 6813–6817.
Szczesny RJ, Obriot H, Paczkowska A, Jedrzejczak R, Dmochowska A, Bartnik E, Formstecher P, Polakowska R, Stepien PP (2007) Down-regulation of human RNA/DNA helicase SUV3 induces apoptosis by a caspase- and AIF-dependent pathway. Biol Cell. 99: 323-332. DOI: 10.1042/BC20060108
Szczesny RJ, Borowski LS, Brzezniak LK, Dmochowska A, Gewartowski K, Bartnik E, Stepien PP (2010) Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance. Nucleic Acids Res 38: 279-298 DOI: 10.1093/nar/gkp903
Veno ST, Kulikowicz T, Pestana C, Stepien PP, Stevnsner T, Bohr VA (2011) The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus. Biochem. J. 440:293–300. DOI: 10.1042/BJ20100991
Wang DD, Guo XE, Modrek AS, Chen CF, Chen PL, Lee WH (2014) Helicase SUV3, polynucleotide phosphorylase, and mitochondrial polyadenylation polymerase form a transient complex to modulate mitochondrial mRNA polyadenylated tail lengths in response to energetic changes. J Biol Chem. 289: 16727-35. DOI: 10.1074/jbc.M113.536540.
Xing JZ, Zhu L, Jackson JA, Gabos S, Sun XJ, Wang XB, Xu X (2005) Dynamic monitoring of cytotoxicity on microelectronic sensors. Chem Res Toxicol. 18: 154-61. DOI: 10.1021/tx049721s
Yogev O, Pines O (2011). Dual targeting of mitochondrial proteins: Mechanism, regulation and function. Biochim Biophys Acta 1808: 1012–1020. DOI: 10.1016/j.bbamem.2010.07.004.
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