Functional insights into long antisense noncoding RNA Kcnq1ot1 mediated bidirectional silencing.
The prevailing view has been that noncoding antisense RNA primarily regulates the transcriptional activity of its sense counterpart, however, a subset of long noncoding antisense RNAs, such as Kcnq1ot1 and Air, have been shown to regulate the transcriptional silencing of multiple genes spread over several hundred kilobases on either side of their promoters. It is however unknown how these long RNAs regulate the transcriptional silencing of multiple genes. Our recent work demonstrated through exploiting an episomal-based system that the Kcnq1ot1 RNA harbors a silencing domain at its 5' end which mediates transcriptional silencing through introducing repressive histone modifications, and by interacting with the chromatin and targeting the associated regions to the perinucleolar space. Based on our current findings as well as previous findings from other labs, we propose a model resembling that of Xist-mediated chromosomal silencing, wherein Kcnq1ot1 RNA initiates transcriptional silencing by coating the flanking chromatin regions and directing the heterochromatin machinery. Maintenance of silencing through subsequent cell divisions would then occur via the targeting of Kcnq1ot1-associated chromatin to the perinucleolar space.
Kanduri
Chandrasekhar
C
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Kanduri.Chandrasekhar@genpat.uu.se
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D008957:Models, Genetic; D016372:RNA, Antisense / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D016372:RNA, Antisense; D022661:RNA, Untranslated