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Pol III binding in six mammals shows conservation among amino acid isotypes despite divergence among tRNA genes

Nature Genetics volume 43, pages 948955 (2011) | Download Citation

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.).

Author information

Author notes

    • Claudia Kutter
    •  & Gordon D Brown

    These authors contributed equally to this work.

Affiliations

  1. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.

    • Claudia Kutter
    • , Gordon D Brown
    • , Michael D Wilson
    • , Stephen Watt
    •  & Duncan T Odom
  2. University of Cambridge, Department of Oncology, Hutchison/Medical Research Council Research Centre, Cambridge, UK.

    • Claudia Kutter
    • , Michael D Wilson
    •  & Duncan T Odom
  3. European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.

    • Ângela Gonçalves
    •  & Alvis Brazma
  4. University of Cambridge, Graduate School of Life Sciences, Cambridge, UK.

    • Ângela Gonçalves
  5. Beatson Institute for Cancer Research, Glasgow, UK.

    • Robert J White
  6. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Duncan T Odom

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Duncan T Odom.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–14 and Supplementary Tables 1 and 8–11

Excel files

  1. 1.

    Supplementary Table 2

    Genomic location of pol III-bound mouse tRNA genes

  2. 2.

    Supplementary Table 3

    Genomic location of pol III-bound rat tRNA genes

  3. 3.

    Supplementary Table 4

    Genomic location of pol III-bound human tRNA genes

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    Supplementary Table 5

    Genomic location of pol III-bound macaque tRNA genes

  5. 5.

    Supplementary Table 6

    Genomic location of pol III-bound dog tRNA genes

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    Supplementary Table 7

    Genomic location of pol III-bound opossum tRNA genes

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DOI

https://doi.org/10.1038/ng.906

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