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

Abstract

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.

RNA 2′-O-Methylation (Nm) Modification in Human Diseases

“…Another enzyme involved in rRNA Nm modification is FTSJ2, one of the two paralogues of FTSJ1 . As already mentioned, FTSJ2 is the human ortholog of the mitochondrial E. coli 23S rRNA 2′-O-methyltransferase (yeast’s Mrm2) [ 52 , 142 ]. FTSJ2 has been implicated in cell proliferation and seen to be overexpressed in different cancer cell lines, especially in lung carcinoma cells [ 53 ].…”

Factors That Shape Eukaryotic tRNAomes: Processing, Modification and Anticodon–Codon Use

“…As these genes are identified solely based on homology and their potential substrate specificities are not known, we cannot rule out that some may modify non-tRNA substrates. Some data indicate that FTSJ2 and FTSJ3 may be involved in modification of mitochondrial and cytoplasmic rRNA, respectively [159,160]. …”

A consistent S-Adenosylmethionine force field improved by dynamic Hirshfeld-I atomic charges for biomolecular simulation

“…This methylation state of PP2A influences a regulatory subunit which controls proteins activity and localization. The human FtsJ homolog 2 is involved in Cell Cycle Control and DNA Repair [37] and Set7/9 is a histone methyltransferase [36] which transfers a methyl group to Lys 4 of the H3 histone. This process is involved in DNA replication and is a possible target to fight diseases like cancer.…”

“…For Set7/9 (PDB code: 1N6A), a histone methyltransferase [36], the dodecahedral water box had a volume of 543 nm 3 , as it contained 16,972 water molecules, 70 sodium ions and 52 chloride ions, and finally the human FtsJ homolog 2 (PDB code: 2NYU) [37] was solvated in a 295 nm 3 dodecahedral water box with 8953 solvent molecules, 29 sodium ions and 32 chloride ions. All three proteins were simulated for 500 ns with the same parameters as described above.…”