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

Oncogene volume 24, pages 5502–5509 (2005)Cite this article

Abstract

tRNA-isopentenyltransferase (tRNA-IPT) catalyses the addition of N6-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 down-regulated 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.

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Acknowledgements

We thank A Hopper for the gift of MT-8 and H57 yeast strains. This work was funded in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) and FIRB, Italy.

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Authors and Affiliations

  1. Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Via G. Venezian 1, Milan, 20133, Italy

    Monica Spinola, Antonella Galvan, Carmen Pignatiello & Tommaso A Dragani

  2. Department of Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy

    Barbara Conti & Ugo Pastorino

  3. Department of Plant Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Bjorn Nicander

  4. Department of Medicine, Surgery and Dental Sciences, University of Milan, San Paolo Hospital, Milan, Italy

    Rita Paroni

Authors
  1. Monica Spinola
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  2. Antonella Galvan
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  3. Carmen Pignatiello
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  5. Ugo Pastorino
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  6. Bjorn Nicander
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  8. Tommaso A Dragani
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Corresponding author

Correspondence to Tommaso A Dragani.

Additional information

Data deposition footnote: Sequence data are available from GenBank under accession numbers AY702933 to AY702947.

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Spinola, M., Galvan, A., Pignatiello, C. et al. Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer. Oncogene 24, 5502–5509 (2005). https://doi.org/10.1038/sj.onc.1208687

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