title: Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation.
abstract: 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.
authors.affiliation: Center for Biological Resources and Informatics, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Makiha
authors.initials: M
authors.lastname: Fukuda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ito
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Inoue
authors.forename: Takahide
authors.initials: T
authors.lastname: Yokoi
authors.forename: Suenori
authors.initials: S
authors.lastname: Chiku
authors.forename: Toutai
authors.initials: T
authors.lastname: Mitsuyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asai
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000235:genetics; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D011506:Proteins; D022661:RNA, Untranslated