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Tiny RNAs associated with transcription start sites in animals

A Corrigendum to this article was published on 01 July 2009

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Abstract

It has been reported that relatively short RNAs of heterogeneous sizes are derived from sequences near the promoters of eukaryotic genes. As part of the FANTOM4 project, we have identified tiny RNAs with a modal length of 18 nt that map within −60 to +120 nt of transcription start sites (TSSs) in human, chicken and Drosophila. These transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the TSS and are preferentially associated with G+C-rich promoters. The 5′ ends of tiRNAs show peak density 10–30 nt downstream of TSSs, indicating that they are processed. tiRNAs are generally, although not exclusively, associated with highly expressed transcripts and sites of RNA polymerase II binding. We suggest that tiRNAs may be a general feature of transcription in metazoa and possibly all eukaryotes.

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Figure 1: Example tiRNA loci.
Figure 2: Distribution and size characteristics of tiRNAs.
Figure 3: Expression of genes with and without tiRNAs.
Figure 4: ChIP-chip enrichment of promoters with tiRNAs.

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  • 26 June 2009

    NOTE: In the version of this article initially published, some author affiliations were incorrectly stated. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank A. Hasegawa, F. Hori, H. Sano for technical assistance. R.J.T. is supported by a US National Science Foundation Graduate Research Fellowship. N.C. is supported by a University of Queensland Postdoctoral Research Fellowship. A.R.R.F. is supported by a CJ Martin Fellowship from the Australian National Health and Medical Research Council (ID 428261). S.M.G. is supported by Australian NH&MRC Fellowship grant no. 455857. V.O. is supported by Telethon TCP00094, Associazione Italiana Riecrca sul Cancro (AIRC), Compagnia San Paolo. J.S.M. is supported by an Australian Research Council Federation Fellowship (ID FF0561986), the University of Queensland and the Queensland State Government. This work was also supported by grants for the Genome Network Project from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Y.H.), and Research Grant for the RIKEN Genome Exploration Research Project from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government, the RIKEN Frontier Research System, Functional RNA Research Program (Y.H.). We thank the reviewers for their insights and suggestions.

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R.J.T. designed the bioinformatic experiments, led the analysis and wrote the manuscript. E.A.G. assisted with the chicken small RNA deep sequencing datasets analysis and helped to write the manuscript. N.C. performed the analysis of THP-1 gene expression. C.S. and S.S. created an in-house database and mapped THP-1 small RNA sequences. G.J.F. analyzed THP-1 promoter architecture. T.L. organized and analyzed THP-1 small RNA sequences. A.R.R.F. and S.M.G. advised on experimental design. K.S., K.I., T.A., M.N., A.K., K.H., C.K., M.M., H.N., S.F., J.K., C.O.D., D.A.H., H.S., V.O., P.C. and Y.H. generated the THP-1 small RNA, deepCAGE, microarray expression, and ChIP-chip data. P.C. and D.A.H. also helped to write the manuscript. J.S.M. helped to design the study and wrote the manuscript. For further information about the small RNA sequencing, contact V.O. (vorlando@vti.telethon.it) or P.C. (carninci@riken.jp). For further information about the bioinformatic analyses, contact R.J.T. (r.taft@imb.uq.edu.au).

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Correspondence to Yoshihide Hayashizaki or John S Mattick.

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Supplementary Figures 1–12, Supplementary Methods, Supplementary Tables 1 and 2 (PDF 4858 kb)

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Taft, R., Glazov, E., Cloonan, N. et al. Tiny RNAs associated with transcription start sites in animals. Nat Genet 41, 572–578 (2009). https://doi.org/10.1038/ng.312

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