Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation.
Characteristics of transformed and tumor cells include increased levels of protein synthesis and elevated expression of RNA polymerase (pol) III products, such as tRNAs and 5S rRNA. However, whether deregulated pol III transcription contributes to transformation has been unclear. Generating cell lines expressing an inducible pol III-specific transcription factor, Brf1, allowed us to raise tRNA and 5S rRNA levels specifically. Brf1 induction caused an increase in cell proliferation and oncogenic transformation, whereas depletion of Brf1 impeded transformation. Among the gene products induced by Brf1 is the tRNA(iMet) that initiates polypeptide synthesis. Overexpression of tRNA(iMet) is sufficient to stimulate cell proliferation and allow immortalized fibroblasts to form foci in culture and tumors in mice. The data indicate that elevated tRNA synthesis can promote cellular transformation.
Marshall
Lynne
L
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Kenneth
Niall S
NS
White
Robert J
RJ
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis; D034622:RNA Interference; D012320:RNA Polymerase III / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000235:genetics* / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D012358:RNA, Transfer, Met; D035361:Transcription Factor TFIIIB; D012320:RNA Polymerase III