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

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_3E1D90E64A12
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Natural antisense transcripts drive a regulatory cascade controlling c-MYC transcription.
Journal
RNA biology
Author(s)
Napoli S., Piccinelli V., Mapelli S.N., Pisignano G., Catapano C.V.
ISSN
1555-8584 (Electronic)
ISSN-L
1547-6286
Publication state
Published
Issued date
02/12/2017
Peer-reviewed
Oui
Volume
14
Number
12
Pages
1742-1755
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
c-MYC, epigenetics, long non coding RNA, natural antisense transcripts, small RNAs, transcriptional regulation
Pubmed
Web of science
Create date
06/09/2017 11:37
Last modification date
20/08/2019 13:34
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