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The regulated retrotransposon transcriptome of mammalian cells

Nature Genetics volume 41, pages 563–571 (2009)Cite this article

Abstract

Although repetitive elements pervade mammalian genomes, their overall contribution to transcriptional activity is poorly defined. Here, as part of the FANTOM4 project, we report that 6–30% of cap-selected mouse and human RNA transcripts initiate within repetitive elements. Analysis of approximately 250,000 retrotransposon-derived transcription start sites shows that the associated transcripts are generally tissue specific, coincide with gene-dense regions and form pronounced clusters when aligned to full-length retrotransposon sequences. Retrotransposons located immediately 5′ of protein-coding loci frequently function as alternative promoters and/or express noncoding RNAs. More than a quarter of RefSeqs possess a retrotransposon in their 3′ UTR, with strong evidence for the reduced expression of these transcripts relative to retrotransposon-free transcripts. Finally, a genome-wide screen identifies 23,000 candidate regulatory regions derived from retrotransposons, in addition to more than 2,000 examples of bidirectional transcription. We conclude that retrotransposon transcription has a key influence upon the transcriptional output of the mammalian genome.

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Figure 1: Patterns of repetitive element expression in mouse and human.
Figure 2: Transcription start site positions in human L1 fragments and full-length copies aligned to a consensus L1 sequence.
Figure 3: Abundance of expressed repetitive elements proximal to known transcripts.
Figure 4: Validation of a SINE-derived alternative promoter in human CSF1R.
Figure 5: Inverse correlation between mean RefSeq CAGE expression and 3′ UTR retrotransposon percentage (x).

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Acknowledgements

G.J.F. is supported by an Australian Postgraduate Award through the Australian government Department of Education, Training and Youth Affairs (DETYA). A.R.R.F. is funded by a CJ Martin Fellowship from the Australian NHMRC (ID 428261). K.S. and K.M.I. are members of the CRC for Chronic Inflammatory Diseases. P.C. and Y.H. are supported by the National Project on Protein Structural and Functional Analysis from MEXT and the National Project on Genome Network Analysis and the RIKEN Genome Exploration Research Project from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government. D.A.H. acknowledges the funding of the ARC Special Research Centre for Functional and Applied Genomics and the NHMRC. S.M.G. holds a Senior Research Fellowship with the Australian NHMRC. N.C. is supported by a UQ postdoctoral research fellowship. V.O. is supported by Telethon Foundation (TCP00094), Associazione Italiana Ricerca sul Cancro (AIRC) and Fondazione Compagnia di San Paolo, and N.H. is supported by an EMBO long-term fellowship.

Author information

Authors and Affiliations

  1. Expression Genomics Laboratory, Institute for Molecular Bioscience, University of Queensland, Queensland, Australia

    Geoffrey J Faulkner, Shivangi Wani, Nicole Cloonan, Anita L Steptoe & Sean M Grimmond

  2. Omics Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan

    Yasumasa Kimura, Carsten O Daub, Charles Plessy, Timo Lassmann, Kazunori Waki, Takahiro Arakawa, Hazuki Takahashi, Jun Kawai, Alistair R R Forrest, Harukazu Suzuki, Yoshihide Hayashizaki & Piero Carninci

  3. Cooperative Research Centre for Chronic Inflammatory Diseases and Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

    Katharine M Irvine & Kate Schroder

  4. Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia at EBRI, Rome, Italy

    Nadine Hornig & Valerio Orlando

  5. Dulbecco Telethon Institute, IGB CNR, Naples, Italy

    Nadine Hornig & Valerio Orlando

  6. The Eskitis Institute for Cell and Molecular Therapies, Griffith University, Australia

    Alistair R R Forrest

  7. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Scotland, UK

    David A Hume

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  1. Geoffrey J Faulkner
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Contributions

G.J.F. led the bioinformatic analysis and drafting of the manuscript. K.M.I., K.S., N.C., A.L.S., T.L., K.W., N.H., T.A., J.K., H.S., Y.H., S.M.G. and P.C. provided data and resources. Y.K., C.O.D. and A.R.R.F. provided bioinformatic analyses. G.J.F. and P.C. designed the experiments. S.W., C.P., A.L.S., H.T. and N.C. performed validation. D.A.H., V.O., S.M.G. and P.C. interpreted data and edited the manuscript. P.C. organized the project.

Corresponding authors

Correspondence to Valerio Orlando, Sean M Grimmond or Piero Carninci.

Supplementary information

Supplementary Text and Figures

Supplementary Note, Supplementary Figures 1–19, Supplementary Tables 1–8 and Supplementary Methods (PDF 1126 kb)

Supplementary Data 1

CAGE library expression clustering by retrotransposon superfamily, family and subfamily (XLS 6576 kb)

Supplementary Data 2

List of putative alternative promoters in human (ZIP 4444 kb)

Supplementary Data 3

List of retrotransposon alternative promoters confirmed by ESTs (XLS 309 kb)

Supplementary Data 4

List of mouse and human RefSeqs containing retrotransposons that overlap exonic sequence (XLS 3624 kb)

Supplementary Data 5

List of human and mouse bidirectional promoter pairs and putative boundary elements (XLS 931 kb)

Supplementary Data 6

List of human bidirectional promoter pairs generating at least one short RNA sequence (XLS 26 kb)

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Faulkner, G., Kimura, Y., Daub, C. et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41, 563–571 (2009). https://doi.org/10.1038/ng.368

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