Abstract
RNA polymerase III (Pol III) transcription of tRNA genes is essential for generating the tRNA adaptor molecules that link genetic sequence and protein translation. By mapping Pol III occupancy genome-wide in mouse, rat, human, macaque, dog and opossum livers, we found that Pol III binding to individual tRNA genes varies substantially in strength and location. However, when we took into account tRNA redundancies by grouping Pol III occupancy into 46 anticodon isoacceptor families or 21 amino acid–based isotype classes, we discovered strong conservation. Similarly, Pol III occupancy of amino acid isotypes is almost invariant among transcriptionally and evolutionarily diverse tissues in mouse. Thus, synthesis of functional tRNA isotypes has been highly constrained, although the usage of individual tRNA genes has evolved rapidly.
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Acknowledgements
We thank J. Hadfield, N. Matthews, S. Aldridge, S. Sayalero, C. Fielding, B. Davis, K. Howe, R. Stark, T. Davidge, S. Ballantyne and M. Nixon. This work was supported by the European Research Council Starting Grant; the European Molecular Biology Organization Young Investigator Award; Hutchinson Whampoa (D.T.O.); Swiss National Science Foundation (C.K.); University of Cambridge (C.K., M.D.W. and D.T.O.); Cancer Research UK (C.K., G.D.B., S.W., M.D.W., R.J.W. and D.T.O.) and European Molecular Biology Laboratory (A.G.).
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C.K., G.D.B. and D.T.O. conceived experiments. C.K., S.W. and M.D.W. carried out experiments. G.D.B., C.K. and A.G. analyzed the data. C.K., G.D.B., A.B., R.J.W. and D.T.O. wrote the paper.
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Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–14 and Supplementary Tables 1 and 8–11 (PDF 1857 kb)
Supplementary Table 2
Genomic location of pol III-bound mouse tRNA genes (XLS 241 kb)
Supplementary Table 3
Genomic location of pol III-bound rat tRNA genes (XLS 99 kb)
Supplementary Table 4
Genomic location of pol III-bound human tRNA genes (XLS 88 kb)
Supplementary Table 5
Genomic location of pol III-bound macaque tRNA genes (XLS 85 kb)
Supplementary Table 6
Genomic location of pol III-bound dog tRNA genes (XLS 65 kb)
Supplementary Table 7
Genomic location of pol III-bound opossum tRNA genes (XLS 81 kb)
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Kutter, C., Brown, G., Gonçalves, Â. et al. Pol III binding in six mammals shows conservation among amino acid isotypes despite divergence among tRNA genes. Nat Genet 43, 948–955 (2011). https://doi.org/10.1038/ng.906
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DOI: https://doi.org/10.1038/ng.906
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