title: Promoter-associated long noncoding RNAs repress transcription through a RNA binding protein TLS.
abstract: The majority of the human genome is found to be transcribed and generates mostly noncoding (nc) RNAs that do not possess protein information. MicroRNAs are one of the well-identified small ncRNAs, but occupy merely a fraction of ncRNAs. Long (large) ncRNAs are emerging as a novel class of ncRNAs, but knowledge of these ncRNAs is far less accumulated. Long ncRNAs are tentatively classified as an ncRNA species containing more than 200 nucleotides. Recently, a long promoter-associated ncRNA (pncRNA) has been identified to be transcribed from the cyclin D1 promoter upon induction by genotoxic factors like ionizing-irradiation. The cyclin D1 pncRNA is specifically bound with an RNA-binding protein TLS (Translocated in liposarcoma) and exerts transcriptional repression through histone acetyltransferase (HAT) inhibitory activity. Analysis of TLS and the pncRNAs could provide a model for elucidating their roles inregulation of mammalian transcriptional programs. The pncRNA binding to TLS turns out to be an essential event for the HAT inhibitory activity. A key consensus sequence of the pncRNA is composed of GGUG, while not every RNA sequence bearing GGUG is targeted by TLS, suggesting that a secondary structure of the GGUG-bearing RNAs is also involved in recognition by TLS. Taken together, TLS is a unique mediator between signals of the long ncRNAs and transcription, suggesting that RNA networking functions in living cells.(1-3).
authors.affiliation: Saitama Medical University, Yamane, Hidaka-shi, Saitama-Ken, Japan. rkurokaw@saitama-med.ac.jp
authors.forename: Riki
authors.initials: R
authors.lastname: Kurokawa
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics; D004249:DNA Damage; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D022661:RNA, Untranslated; D034702:RNA-Binding Protein FUS; D019938:Cyclin D1; D051548:Histone Acetyltransferases