Abstract

tRNA-isopentenyltransferase (tRNA-IPT) catalyses the addition of N-6-isopentenyladenosine (i(6)A) 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

Published in

Oncogene
2005, Volume: 24, number: 35, pages: 5502-5509
Publisher: NATURE PUBLISHING GROUP

SLU Authors

• Nicander, Björn

  • Department of Plant Biology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Food Science
Environmental Sciences related to Agriculture and Land-use


Publication identifier

DOI: https://doi.org/10.1038/sj.onc.1208687

Permanent link to this page (URI)

https://res.slu.se/id/publ/8497