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2017 | 64 | 1 | 177-181
Article title

Human SUV3 helicase regulates growth rate of the HeLa cells and can localize in the nucleoli

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The human SUV3 helicase (SUV3, hSUV3, SUPV3L1) is a DNA/RNA unwinding enzyme belonging to the class of DexH-box helicases. It localizes predominantly in the mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome with exonuclease PNP (polynucleotide phosphorylase). Association of this complex with the polyA polymerase can modulate 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 the 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 have designed gene constructs able to inhibit the SUV3 activity exclusively in the cell nuclei. 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 the SUV3 gene resulted in a higher growth rate. In addition, we demonstrate that the SUV3 helicase can be found in the HeLa cell nucleoli, but it is not detectable in the DNA-repair foci. Our results indicate that the nucleolar-associated human SUV3 protein is an important factor in regulation of the cell cycle.
Physical description
  • Institute of Genetics and Biotechnology, Faculty of Biology, Warsaw University, Warsaw, Poland
  • Centre for New Technologies, University of Warsaw, Warsaw, Poland
  • Institute of Genetics and Biotechnology, Faculty of Biology, Warsaw University, Warsaw, Poland
  • Department of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
  • Department of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
  • Institute of Genetics and Biotechnology, Faculty of Biology, Warsaw University, Warsaw, Poland
  • Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
  • Centre for New Technologies, University of Warsaw, Warsaw, Poland
  • 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: 1223-1240. 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: 1193-1201. 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: 155-162.
  • Dziembowski A, Piwowarski J, Hoser R, Minczuk M, Dmochowska A, Siep M, van der Spek 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: 313-322. doi: 10.1177/1087057110397359.
  • Macovei A, Sahoo RK, Fae M, Balestrazzi A, Carbonera D, Tuteja N, (2016) Overexpression of PDH45 or SUV3 helicases in rice leads to delayed leaf senescence-associated events. Protoplasma published on-line. DOI 10.1007/s00709-016-1017-4.
  • 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 SUV3 helicase in the mitochondrial matrix and its preferential unwinding of dsDNA. Nucleic Acids Res 30: 5074-5086.
  • Paul E, Cronan R, Weston PJ, Boekelheide K, Sedivy JM, Lee SY, Wiest DL, Resnick MB, Klysik JE (2009) Disruption of Supv3L1 damages the skin and causes sarcopenia, loss of fat, and death. 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: 609-617. 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: 1184-1193. 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: 1040-1047. 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 SUV3 helicase in RNA surveillance. Nucleic Acids Res 38: 279-298. doi: 10.1093/nar/gkp903.
  • Tsai RY, Pederson T (2016) Connecting the nucleolus to the cell cycle and human disease. FASEB J 28: 3290-3296. doi: 10.1096/fj.14-254680.
  • 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: 16727-16735. 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: 154-161. 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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