Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs.
Chromatin remodeling guided by non-coding RNA (ncRNA) contributes mechanistically to the establishment of chromatin structure and to the maintenance of epigenetic memory. Various ncRNAs have been identified as regulators of chromatin structure and gene expression. The widespread occurrence of antisense transcription in eukaryotes emphasizes the prevalence of gene regulation by natural antisense transcripts. Recently, antisense ncRNAs have been implicated in the silencing of tumor suppressor genes through epigenetic remodeling events. Characterization of the antisense RNAs involved in the development or maintenance of oncogenic states may define ncRNAs as early biomarkers for the emergence of cancer, and could have a significant impact on the development of tools for disease diagnosis and treatment. In this review, current knowledge on the mechanisms of ncRNA-mediated transcriptional gene silencing in humans is discussed, and parallels between the establishment of a silent chromatin state mediated by siRNAs and long antisense ncRNAs are highlighted.
Malecová
Barbora
B
The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. malecova@scripps.edu
Morris
Kevin V
KV
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D018392:Genomic Imprinting; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D049951:X Chromosome Inactivation / Q000235:genetics
D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins