Analysis of Small Human Proteins Reveals the Translation of Upstream Open Reading Frames of mRNAs

  1. Masaaki Oyama1,
  2. Chiharu Itagaki2,
  3. Hiroko Hata3,
  4. Yutaka Suzuki1,
  5. Tomonori Izumi2,
  6. Tohru Natsume4,
  7. Toshiaki Isobe2, and
  8. Sumio Sugano1,5
  1. 1 Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
  2. 2 Division of Proteomics Research, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
  3. 3 Division of Cancer Genomics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
  4. 4 National Institute of Advanced Industrial Science and Technology, Biological Information Research Center (JBIRC), Koutoh-ku, Tokyo 135-0064, Japan

Abstract

To find novel short coding sequences from accumulated full-length cDNA sequences, proteomic analysis of small proteins expressed in human leukemia K562 cells was performed using high-resolution nanoflow liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Our analysis led to the identification of 54 proteins not more than 100 amino acids in length, including four novel ones. These novel short coding sequences were all located upstream of the longest open reading frame (ORF) of the corresponding cDNA. Our findings indicate that the translation of short ORFs occurs in vivo whether or not there exists a longer coding region in the downstream of the mRNA. This investigation provides the first direct evidence of translation of upstream ORFs in human cells, which could greatly change the current outline of the human proteome.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2384604.

  • 5 Corresponding author. E-MAIL ssugano{at}ims.u-tokyo.ac.jp; FAX 81-3-5449-5416.

    • Accepted April 9, 2004.
    • Received January 23, 2004.
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