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Nucleic Acids Research Advance Access published online on June 16, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp426
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© 2009 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.

Molecular Biology

Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation

Kunio Kikuchi1, Makiha Fukuda2, Tomoya Ito2, Mitsuko Inoue2, Takahide Yokoi3, Suenori Chiku4, Toutai Mitsuyama5, Kiyoshi Asai5,6, Tetsuro Hirose7 and Yasunori Aizawa1,*

1Center for Biological Resources and Informatics, 2Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, 3Hitachi Software Engineering Co., Ltd., Yokohama 230-0045, 4Science Solutions Division, Mizuho Information and Research Institute, Inc., Tokyo 101-8443, 5Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, 6Department of Computational Biology, Graduate School of Frontier Sciences, the University of Tokyo, Chiba 277-8561 and 7Functional RNomics Team, Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, Japan

*To whom correspondence should be addressed. Tel/Fax: +81 45 924 5787; Email: yaizawa{at}bio.titech.ac.jp

Received April 7, 2009. Revised April 7, 2009. Accepted May 8, 2009.

Mammalian transcriptome analysis has uncovered tens of thousands of novel transcripts of unknown function (TUFs). Classical and recent examples suggest that the majority of TUFs may underlie vital intracellular functions as non-coding RNAs because of their low coding potentials. However, only a portion of TUFs have been studied to date, and the functional significance of TUFs remains mostly uncharacterized. To increase the repertoire of functional TUFs, we screened for TUFs whose expression is controlled during differentiation of pluripotent human mesenchymal stem cells (hMSCs). The resulting six TUFs, named transcripts related to hMSC differentiation (TMDs), displayed distinct transcriptional kinetics during hMSC adipogenesis and/or osteogenesis. Structural and comparative genomic characterization suggested a wide variety of biologically active structures of these TMDs, including a long nuclear non-coding RNA, a microRNA host gene and a novel small protein gene. Moreover, the transcriptional response to established pathway activators indicated that most of these TMDs were transcriptionally regulated by each of the two key pathways for hMSC differentiation: the Wnt and protein kinase A (PKA) signaling pathways. The present study suggests that not only TMDs but also other human TUFs may in general participate in vital cellular functions with different molecular mechanisms.


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