Nucleic Acids Research Advance Access originally published online on May 14, 2008
Nucleic Acids Research 2008 36(11):3707-3715; doi:10.1093/nar/gkn248
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Nucleic Acids Research, 2008, Vol. 36, No. 11 3707-3715
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Comprehensive detection of human terminal oligo-pyrimidine (TOP) genes and analysis of their characteristics
1Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, 2Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562 and 3Institute for Bioinformatics Research and Development (BIRD), Japan Science and Technology Agency (JST), 4-5-3 Chiyoda-ku, Tokyo, Japan
*To whom correspondence should be addressed. Tel: +81 3 5449 5131; Fax: +81 3 5449 5133; Email: knakai{at}ims.u-tokyo.ac.jp
Received December 29, 2007. Revised March 25, 2008. Accepted April 17, 2008.
Although the knowledge accumulated on the transcriptional regulations of eukaryotes is significant, the knowledge on their translational regulations remains limited. Thus, we performed a comprehensive detection of terminal oligo-pyrimidine (TOP), which is one of the well-characterized cis-regulatory motifs for translational controls located immediately downstream of the transcriptional start sites of mRNAs. Utilizing our precise 5'-end information of the full-length cDNAs, we could screen 1645 candidate TOP genes by position specific matrix search. Among them, not only 75 out of 78 ribosomal protein genes but also eight previously identified non-ribosomal-protein TOP genes were included. We further experimentally validated the translational activities of 83 TOP candidate genes. Clear translational regulations exerted on the stimulation of 12-O-tetradecanoyl-1-phorbol-13-acetate for at least 41 of them was observed, indicating that there should be a few hundreds of human genes which are subjected to regulation at translation levels via TOPs. Our result suggests that TOP genes code not only formerly characterized ribosomal proteins and translation-related proteins but also a wider variety of proteins, such as lysosome-related proteins and metabolism-related proteins, playing pivotal roles in gene expression controls in the majority of cellular mRNAs.