Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters
Tiffany Hung,Yulei Wang,Michael F. Lin,Michael F. Lin,Ashley K. Koegel,Yojiro Kotake,Yojiro Kotake,Gavin D. Grant,Hugo M. Horlings,Nilay Shah,Christopher B. Umbricht,Pei Wang,Yu Wang,Benjamin Kong,Anita Langerød,Anne Lise Børresen-Dale,Seung K. Kim,Marc J. van de Vijver,Saraswati Sukumar,Michael L. Whitfield,Manolis Kellis,Manolis Kellis,Yue Xiong,David J. Wong,Howard Y. Chang +24 more
TLDR
In this article, an ultra-high-density array that tiles the promoters of 56 cell-cycle genes was used to interrogate 108 samples representing diverse perturbations, identifying 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle.Abstract:
Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.read more
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Molecular Mechanisms of Long Noncoding RNAs
Kevin C. Wang,Howard Y. Chang +1 more
TL;DR: These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution.
Journal ArticleDOI
Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
Moran N. Cabili,Cole Trapnell,Cole Trapnell,Loyal A. Goff,Magdalena J. Koziol,Magdalena J. Koziol,Barbara Tazon-Vega,Barbara Tazon-Vega,Aviv Regev,John L. Rinn,John L. Rinn +10 more
TL;DR: It is found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that l incRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes.
Journal ArticleDOI
Genome Regulation by Long Noncoding RNAs
John L. Rinn,Howard Y. Chang +1 more
TL;DR: Long noncoding RNAs (lncRNAs) as discussed by the authors form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome.
Journal ArticleDOI
Long non-coding RNAs: new players in cell differentiation and development
Alessandro Fatica,Irene Bozzoni +1 more
TL;DR: The function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development are described.
Journal ArticleDOI
Long Noncoding RNAs in Cancer Pathways
Adam M. Schmitt,Howard Y. Chang +1 more
TL;DR: It is understood that lncRNAs drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein, and RNA, making these molecules attractive targets for therapeutic intervention in the fight against cancer.
References
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Rajnish A. Gupta,Nilay Shah,Kevin C. Wang,Jeewon Kim,Hugo M. Horlings,David J. Wong,Miao-Chih Tsai,Tiffany Hung,Pedram Argani,John L. Rinn,Yulei Wang,Pius Brzoska,Benjamin Kong,Rui-Chun Li,Robert B. West,Marc J. van de Vijver,Saraswati Sukumar,Howard Y. Chang +17 more
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