FTSJ2, a Heat Shock-Inducible Mitochondrial Protein, Suppresses Cell Invasion and Migration

Ribosomal RNA large subunit methyltransferase J (RrmJ), an Escherichia coli heat shock protein, is responsible for 2′-O-ribose methylation in 23S rRNA. In mammals, three close homologs of RrmJ have been identified and have been designated as FTSJ1, FTSJ2 and FTSJ3; however, little is known about these genes. In this study, we characterized the mammalian FTSJ2, which was the most related protein to RrmJ in a phylogenetic analysis that had similar amino acid sequence features and tertiary protein structures of RrmJ. FTSJ2 was first identified in this study as a nucleus encoded mitochondrial protein that preserves the heat shock protein character in mammals in which the mRNA expressions was increased in porcine lung tissues and A549 cells after heat shock treatment. In addition, a recent study in non-small cell lung cancer (NSCLC) suggested that the FTSJ2 gene is located in a novel oncogenic locus. However, our results demonstrate that the expression of FTSJ2 mRNA was decreased in the more invasive subline (CL1-5) of the lung adenocarcinoma cells (CL1) compared with the less invasive subline (CL1-0), and overexpression of FTSJ2 resulted in the inhibition of cell invasion and migration in the rhabdomyosarcoma cell (TE671). In conclusion, our findings indicate that mammalian FTSJ2 is a mitochondrial ortholog of E. coli RrmJ and conserves the heat shock protein properties. Moreover, FTSJ2 possesses suppressive effects on the invasion and migration of cancer cells.

[1]  J. Bujnicki,et al.  MRM2 encodes a novel yeast mitochondrial 21S rRNA methyltransferase , 2002, The EMBO journal.

[2]  Eun Hee Lee,et al.  Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer , 2013, Virchows Archiv.

[3]  M. Hendrix,et al.  Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. , 1997, American journal of respiratory cell and molecular biology.

[4]  E. Binet,et al.  Translational defects of Escherichia coli mutants deficient in the Um(2552) 23S ribosomal RNA methyltransferase RrmJ/FTSJ. , 2000, Biochemical and biophysical research communications.

[5]  Ying Zhou,et al.  Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovarian cancer cells. , 2012, Cancer letters.

[6]  Aoife McLysaght,et al.  Porter: a new, accurate server for protein secondary structure prediction , 2005, Bioinform..

[7]  B. Lapeyre.  Conserved ribosomal RNA modification and their putative roles in ribosome biogenesis and translation , 2004 .

[8]  J. Gécz,et al.  Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. , 2004, American journal of human genetics.

[9]  Yu-Tang Tung,et al.  Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor. , 2013, Journal of dairy science.

[10]  N. Sakamoto,et al.  Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase , 2013, Journal of Virology.

[11]  R. Morimoto,et al.  Molecular chaperones and the stress of oncogenesis , 2004, Oncogene.

[12]  E. Craig,et al.  The heat shock response. , 1985, CRC critical reviews in biochemistry.

[13]  M. Ristow,et al.  Mitochondria and metabolic homeostasis. , 2013, Antioxidants & redox signaling.

[14]  D. Boisvert,et al.  Crystal structure of a fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 Å resolution , 2000, The EMBO journal.

[15]  R. Mache,et al.  Structure and transcription of the 5S rRNA gene from spinach chloroplasts , 2004, Current Genetics.

[16]  M. Widerak,et al.  U2552 methylation at the ribosomal A-site is a negative modulator of translational accuracy. , 2005, Gene.

[17]  Anders Liljas,et al.  Crystal structure of catechol O-methyltransferase , 1994, Nature.

[18]  Hsiao‐Ling Chen,et al.  Production of recombinant porcine colipase secreted by Pichia pastoris and its application to improve dietary fat digestion and growth of postweaning piglets , 2008, Biotechnology progress.

[19]  Juan Zhang,et al.  Mitochondrial dynamics regulates migration and invasion of breast cancer cells , 2012, Oncogene.

[20]  D. Kressler,et al.  Spb1p Is a Yeast Nucleolar Protein Associated with Nop1p and Nop58p That Is Able To BindS-Adenosyl-l-Methionine In Vitro , 2000, Molecular and Cellular Biology.

[21]  Luis G. Morello,et al.  The Human Nucleolar Protein FTSJ3 Associates with NIP7 and Functions in Pre-rRNA Processing , 2011, PloS one.

[22]  J. Puglisi,et al.  Solution structure of the A loop of 23S ribosomal RNA , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Georgopoulos,et al.  Biological role and regulation of the universally conserved heat shock proteins. , 1991, The Journal of biological chemistry.

[24]  D. Kressler,et al.  Spb1p is a putative methyltransferase required for 60S ribosomal subunit biogenesis in Saccharomyces cerevisiae. , 1999, Nucleic acids research.

[25]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[26]  Jakub Pas,et al.  Molecular phylogenetics of the RrmJ/fibrillarin superfamily of ribose 2'-O-methyltransferases. , 2003, Gene.

[27]  D. McMillan,et al.  Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. , 1998, Circulation research.

[28]  G. Lutfalla,et al.  Functional redundancy of Spb1p and a snR52-dependent mechanism for the 2'-O-ribose methylation of a conserved rRNA position in yeast. , 2003, Molecular cell.

[29]  E. Fauman,et al.  RNA methylation under heat shock control. , 2000, Molecular cell.

[30]  M. Siegelin.  Inhibition of the mitochondrial Hsp90 chaperone network: a novel, efficient treatment strategy for cancer? , 2013, Cancer letters.

[31]  Yu-Tang Tung,et al.  Treadmill running upregulates the expression of acetylcholine receptor in rat gastrocnemius following botulinum toxin A injection , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[32]  T. Yagi,et al.  Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. , 2013, The Journal of clinical investigation.

[33]  E. Binet,et al.  The FtsJ/RrmJ Heat Shock Protein of Escherichia coli Is a 23 S Ribosomal RNA Methyltransferase* , 2000, The Journal of Biological Chemistry.

[34]  Jeremy J. W. Chen,et al.  Tumor and Stem Cell Biology Cancer Research Tumor Suppressor HLJ 1 Binds and Functionally Alters Nucleophosmin via Activating Enhancer Binding Protein 2 α Complex Formation , 2010 .

[35]  Hsiao‐Ling Chen,et al.  Probiotic Lactobacillus casei Expressing Human Lactoferrin Elevates Antibacterial Activity in the Gastrointestinal Tract , 2010, BioMetals.

[36]  F A Quiocho,et al.  Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme. , 1998, Molecular cell.

[37]  S. K. Purushothaman,et al.  Spb1p-directed formation of Gm2922 in the ribosome catalytic center occurs at a late processing stage. , 2004, Molecular cell.

[38]  Yu-Tang Tung,et al.  Active Component of Danshen (Salvia miltiorrhiza Bunge), Tanshinone I, Attenuates Lung Tumorigenesis via Inhibitions of VEGF, Cyclin A, and Cyclin B Expressions , 2013, Evidence-based complementary and alternative medicine : eCAM.

[39]  Janusz M Bujnicki,et al.  Trm7p catalyses the formation of two 2′‐O‐methylriboses in yeast tRNA anticodon loop , 2002, The EMBO journal.

[40]  Yu-Tang Tung,et al.  Application of porcine lipase secreted by pichia pastoris to improve fat digestion and growth performance of postweaning piglets. , 2010, Journal of agricultural and food chemistry.

[41]  W. Boelens,et al.  Expression of small heat shock proteins HspB2, HspB8, Hsp20 and cvHsp in different tissues of the perinatal developing pig. , 2003, European journal of cell biology.

[42]  Luis G. Morello,et al.  Proteomic characterization of the human FTSJ3 preribosomal complexes. , 2012, Journal of proteome research.

[43]  C R Woese,et al.  Mitochondrial origins. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Glasner,et al.  Genome-wide expression profiling in Escherichia coli K-12. , 1999, Nucleic acids research.

[45]  Yau-Huei Wei,et al.  High Mitochondrial DNA Copy Number and Bioenergetic Function Are Associated with Tumor Invasion of Esophageal Squamous Cell Carcinoma Cell Lines , 2012, International journal of molecular sciences.

[46]  Haichao Wang,et al.  The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics , 2014, Oncogene.

[47]  S. Morimura,et al.  Structure and function of the ftsH gene in Escherichia coli. , 1991, Research in microbiology.

[48]  U. Jakob,et al.  Active Site in RrmJ, a Heat Shock-induced Methyltransferase* , 2002, The Journal of Biological Chemistry.

[49]  Bradley P. Coe,et al.  Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer. , 2008, Genome.

[50]  X. Zhuang,et al.  PINK1 Deficiency Attenuates Astrocyte Proliferation Through Mitochondrial Dysfunction, Reduced AKT and Increased p38 MAPK Activation, and Downregulation of EGFR , 2013, Glia.