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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 948–955 (2011)Cite this article

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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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Figure 1: Pol III occupies and transcribes tRNA genes in mouse liver.
Figure 2: tRNA isoacceptors and isotypes are differentially bound by Pol III in mouse liver.
Figure 3: Amino acid isotypes are bound by Pol III in a tissue-independent manner.
Figure 4: The tRNA genes bound by Pol III diverge in genomic location and functional usage among mammals.
Figure 5: Pol III occupancy and codon usage across mammalian evolution.

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References

  1. Chan, E.T. et al. Conservation of core gene expression in vertebrate tissues. J. Biol. 8, 33 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  2. Guttman, M. et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Marques, A.C. & Ponting, C.P. Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness. Genome Biol. 10, R124 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  4. Meader, S., Ponting, C.P. & Lunter, G. Massive turnover of functional sequence in human and other mammalian genomes. Genome Res. 20, 1335–1343 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Odom, D.T. et al. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat. Genet. 39, 730–732 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Bourque, G. et al. Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res. 18, 1752–1762 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Schmidt, D. et al. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328, 1036–1040 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Kunarso, G. et al. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat. Genet. 42, 631–634 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Barski, A. et al. Pol II and its associated epigenetic marks are present at Pol III–transcribed noncoding RNA genes. Nat. Struct. Mol. Biol. 17, 629–634 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Canella, D., Praz, V., Reina, J.H., Cousin, P. & Hernandez, N. Defining the RNA polymerase III transcriptome: Genome-wide localization of the RNA polymerase III transcription machinery in human cells. Genome Res. 20, 710–721 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Moqtaderi, Z. et al. Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells. Nat. Struct. Mol. Biol. 17, 635–640 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Oler, A.J. et al. Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat. Struct. Mol. Biol. 17, 620–628 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Raha, D. et al. Close association of RNA polymerase II and many transcription factors with Pol III genes. Proc. Natl. Acad. Sci. USA 107, 3639–3644 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kindler, S., Wang, H., Richter, D. & Tiedge, H. RNA transport and local control of translation. Annu. Rev. Cell Dev. Biol. 21, 223–245 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Lowe, T.M. & Eddy, S.R. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 25, 955–964 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Goodenbour, J.M. & Pan, T. Diversity of tRNA genes in eukaryotes. Nucleic Acids Res. 34, 6137–6146 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Plotkin, J.B. & Kudla, G. Synonymous but not the same: the causes and consequences of codon bias. Nat. Rev. Genet. 12, 32–42 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. White, R.J. Transcription by RNA polymerase III: more complex than we thought. Nat. Rev. Genet. 12, 459–463 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. Dieci, G., Fiorino, G., Castelnuovo, M., Teichmann, M. & Pagano, A. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614–622 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Muse, G.W. et al. RNA polymerase is poised for activation across the genome. Nat. Genet. 39, 1507–1511 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Zeitlinger, J. et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat. Genet. 39, 1512–1516 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Davuluri, R.V., Suzuki, Y., Sugano, S., Plass, C. & Huang, T.H. The functional consequences of alternative promoter use in mammalian genomes. Trends Genet. 24, 167–177 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Keren, H., Lev-Maor, G. & Ast, G. Alternative splicing and evolution: diversification, exon definition and function. Nat. Rev. Genet. 11, 345–355 (2010).

    Article  CAS  PubMed  Google Scholar 

  24. Coughlin, D.J., Babak, T., Nihranz, C., Hughes, T.R. & Engelke, D.R. Prediction and verification of mouse tRNA gene families. RNA Biol. 6, 195–202 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Haeusler, R.A., Pratt-Hyatt, M., Good, P.D., Gipson, T.A. & Engelke, D.R. Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. Genes Dev. 22, 2204–2214 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Dittmar, K.A., Goodenbour, J.M. & Pan, T. Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2, e221 (2006).

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kanaya, S., Yamada, Y., Kudo, Y. & Ikemura, T. Studies of codon usage and tRNA genes of 18 unicellular organisms and quantification of Bacillus subtilis tRNAs: gene expression level and species-specific diversity of codon usage based on multivariate analysis. Gene 238, 143–155 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Plotkin, J.B., Robins, H. & Levine, A.J. Tissue-specific codon usage and the expression of human genes. Proc. Natl. Acad. Sci. USA 101, 12588–12591 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sémont, A. et al. Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury. Adv. Exp. Med. Biol. 585, 19–30 (2006).

    Article  PubMed  Google Scholar 

  30. Blouin, A., Bolender, R.P. & Weibel, E.R. Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study. J. Cell Biol. 72, 441–455 (1977).

    Article  CAS  PubMed  Google Scholar 

  31. Romer, A.S. & Parsons, T.S . The Vertebrate Body (Saunders College Pub., Philadelphia, 1986).

  32. Gibbs, R.A. et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428, 493–521 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Lindblad-Toh, K. et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438, 803–819 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Rogers, H.H., Bergman, C.M. & Griffiths-Jones, S. The evolution of tRNA genes in Drosophila. Genome Biol. Evol. 2, 467–477 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  35. Willis, I.M. RNA polymerase III. Genes, factors and transcriptional specificity. Eur. J. Biochem. 212, 1–11 (1993).

    Article  CAS  PubMed  Google Scholar 

  36. Paten, B., Herrero, J., Beal, K., Fitzgerald, S. & Birney, E. Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs. Genome Res. 18, 1814–1828 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Paten, B., Herrero, J., Beal, K. & Birney, E. Sequence progressive alignment, a framework for practical large-scale probabilistic consistency alignment. Bioinformatics 25, 295–301 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. Chiaromonte, F., Yap, V.B. & Miller, W. Scoring pairwise genomic sequence alignments. Pac. Symp. Biocomput. 7, 115–126 (2002).

    Google Scholar 

  39. Kent, W.J., Baertsch, R., Hinrichs, A., Miller, W. & Haussler, D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl. Acad. Sci. USA 100, 11484–11489 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Man, O. & Pilpel, Y. Differential translation efficiency of orthologous genes is involved in phenotypic divergence of yeast species. Nat. Genet. 39, 415–421 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Duret, L. & Galtier, N. Biased gene conversion and the evolution of mammalian genomic landscapes. Annu. Rev. Genomics Hum. Genet. 10, 285–311 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Thompson, M., Haeusler, R.A., Good, P.D. & Engelke, D.R. Nucleolar clustering of dispersed tRNA genes. Science 302, 1399–1401 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Gerstein, M.B. et al. Integrative analysis of the Caenorhabditis elegans Genome by the modENCODE project. Science 330, 1775–1787 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Kasowski, M. et al. Variation in transcription factor binding among humans. Science 328, 232–235 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Roy, S. et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330, 1787–1797 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Gandhi, S.J., Zenklusen, D., Lionnet, T. & Singer, R.H. Transcription of functionally related constitutive genes is not coordinated. Nat. Struct. Mol. Biol. 18, 27–34 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Schmidt, D. et al. ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions. Methods 48, 240–248 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Fairley, J.A., Scott, P.H. & White, R.J. TFIIIB is phosphorylated, disrupted and selectively released from tRNA promoters during mitosis in vivo. EMBO J. 22, 5841–5850 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L. & Wold, B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5, 621–628 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Lemon, J. Plotrix: a package in the red light district of R. R-News, 6, 8–13 (2006).

    Google Scholar 

  52. Schwartz, S. et al. Human-mouse alignments with BLASTZ. Genome Res. 13, 103–107 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Waterston, R.H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S.L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  55. Turro, E. et al. Haplotype and isoform specific expression estimation using multi-mapping RNA-seq reads. Genome Biol. 12, R13 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Robinson, M.D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

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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

  1. Claudia Kutter and Gordon D Brown: These authors contributed equally to this work.

Authors and 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. Department of Oncology, University of Cambridge, 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.

Corresponding author

Correspondence to Duncan T Odom.

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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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