Long-Range Heterogeneity at the 3′ Ends of Human mRNAs

  1. Christian Iseli1,2,6,
  2. Brian J. Stevenson1,2,6,
  3. Sandro J. de Souza4,
  4. Helena B. Samaia4,
  5. Anamaria A. Camargo4,
  6. Kenneth H. Buetow5,
  7. Robert L. Strausberg5,
  8. Andrew J.G. Simpson4,
  9. Philipp Bucher2,3, and
  10. C. Victor Jongeneel1,2,7
  1. 1Office of Information Technology, Ludwig Institute for Cancer Research; 2Swiss Institute of Bioinformatics; and 3Swiss Institute for Experimental Cancer Research, Switzerland; 4Ludwig Institute for Cancer Research, São Paulo 01509-010, SP, Brazil; 5National Cancer Institute, Bethesda, Maryland 20892, USA

Abstract

The publication of a draft of the human genome and of large collections of transcribed sequences has made it possible to study the complex relationship between the transcriptome and the genome. In the work presented here, we have focused on mapping mRNA 3′ ends onto the genome by use of the raw data generated by the expressed sequence tag (EST) sequencing projects. We find that at least half of the human genes encode multiple transcripts whose polyadenylation is driven by multiple signals. The corresponding transcript 3′ ends are spread over distances in the kilobase range. This finding has profound implications for our understanding of gene expression regulation and of the diversity of human transcripts, for the design of cDNA microarray probes, and for the interpretation of gene expression profiling experiments.

[The following individuals kindly provided reagents, samples or unpublished information as indicated in the paper: G. Riggins, C. Ruegg, J.-B. Demoulin, P. Olsson, F. Funari, P. Schneider, L.F. Reis, and J.-C. Renauld]

Footnotes

  • 6 These authors contributed equally to this work.

  • 7 Corresponding author: E-mail ; FAX 41 21 692 5945.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.62002. Article published online before print in June 2002.

    • Received January 9, 2002.
    • Accepted April 3, 2002.
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