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Non‐coding RNAs; epigenetic regulators of gene transcription in human cells
Author(s) -
Morris Kevin V
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.333.2
Subject(s) - pseudogene , biology , epigenetics , gene silencing , enhancer , gene , effector , regulation of gene expression , rna , non coding rna , genetics , rna interference , long non coding rna , gene expression , rna silencing , transcription (linguistics) , antisense rna , microbiology and biotechnology , genome , linguistics , philosophy
Recent observations have demonstrated that exogenously introduced small antisense RNAs (asRNAs) can transcriptionally modulate gene expression in human cells. The mechanism involved in small asRNA directed transcriptional gene silencing (TGS) appears to involve DNA methyltransferase 3a (DNMT3a). However, an endogenous RNA trigger directing epigenetic regulatory proteins to targeted genomic loci in human cells has remained unknown. We present evidence here suggesting that long non‐coding asRNAs function in human cells as effector molecules driving TGS. These asRNAs, in some cases emanating from pseudogenes, function to guide epigenetic remodeling complexes consisting of Enhancer of Zeste (Ezh2) and DNMT3a to target loci. When these regulatory asRNAs are degraded using RNAi the result can be a concomitant activation of their protein‐coding counter part. Importantly, this RNA based transcriptional regulatory mechanism can be taken advantage of to either transcriptionally silence a genes expression in a long‐term manner or activate a genes transcription by the targeted degradation of the regulatory long antisense non‐coding RNAs.