Natural antisense transcripts drive a regulatory cascade controlling c-MYC transcription

Cis-natural antisense transcripts (cis-NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. cis-NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe t...

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Bibliographic Details
Published in:	RNA biology Vol. 14; no. 12; pp. 1742 - 1755
Main Authors:	Napoli, Sara, Piccinelli, Valentina, Mapelli, Sarah N., Pisignano, Giuseppina, Catapano, Carlo V.
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 02-12-2017
Subjects:	3' Untranslated Regions Acetylation c-MYC Cell Line, Tumor Cloning, Molecular Epigenesis, Genetic epigenetics Gene Expression Regulation Genes, myc Genetic Loci Histones - metabolism Humans long non coding RNA Models, Biological natural antisense transcripts Nucleic Acid Conformation Research Paper Ribonuclease III - metabolism RNA, Antisense - genetics RNA, Untranslated - genetics small RNAs Transcription Initiation Site Transcription, Genetic transcriptional regulation natural antisense transcripts long non coding RNA c-MYC transcriptional regulation epigenetics small RNAs
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Summary:	Cis-natural antisense transcripts (cis-NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. cis-NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe the presence of cis-NATs in the 3′ distal region of the c-MYC locus and investigate their impact on transcriptional regulation of this key oncogene in human cancers. We found that cis-NATs are produced as consequence of the activation of cryptic transcription initiation sites in the 3′ distal region downstream of the c-MYC 3′UTR. The process is tightly regulated and leads to the formation of two main transcripts, NAT6531 and NAT6558, which differ in their ability to fold into stem-loop secondary structures. NAT6531 acts as a substrate for DICER and as a source of small RNAs capable of modulating c-MYC transcription. This complex system, based on the interplay between cis-NATs and NAT-derived small RNAs, may represent an important layer of epigenetic regulation of the expression of c-MYC and other genes in human cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Supplemental data for this article can be accessed on the publisher's website.
ISSN:	1547-6286 1555-8584
DOI:	10.1080/15476286.2017.1356564