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 © 2011 Landes Bioscience and Springer Science+Business Media, LLC.