Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer

Monica Spinola, Antonella Galvan, Carmen Pignatiello, Barbara Conti, Ugo Pastorino, Bjorn Nicander, Rita Paroni, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

tRNA-isopentenyltransferase (tRNA-IPT) catalyses the addition of N 6-isopentenyladenosine (i6A) on residue 37 of tRNA molecules that bind codons starting with uridine. Post-transcriptional modifications of tRNA molecules have been demonstrated to be essential in maintaining the correct reading frame of the translational machinery, thus improving fidelity and efficiency of protein synthesis. We show here that the human tRNA-isopentenyltransferase (TRIT1) gene encodes a complex pattern of mRNA variants through alternative splicing in both normal and tumor lung tissue and that the nonsense suppressor activity of tRNA-IPT is maintained only in the full-length mRNA isoform, as revealed by gene complementation in yeast. Expression of the full-length transcript was downregulated 6-14-fold in lung adenocarcinomas as compared to normal lung tissue. A549 lung cancer cells transfected to express the functional TRIT1 gene formed significantly smaller colonies with reduced scattering on the edges and had only limited ability to induce tumors in nude mice. Our findings raise the possibility of TRIT1 as a candidate lung tumor suppressor.

Original languageEnglish
Pages (from-to)5502-5509
Number of pages8
JournalOncogene
Volume24
Issue number35
DOIs
Publication statusPublished - Aug 18 2005

Keywords

  • Disease models
  • Lung cancer
  • Nonsense suppressor
  • Tumor suppressor genes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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