Journal
RNA BIOLOGY
Volume 14, Issue 12, Pages 1742-1755Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2017.1356564
Keywords
c-MYC; epigenetics; long noncoding RNA; natural antisense transcripts; small RNAs; transcriptional regulation
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Funding
- Swiss National Science Foundation [310030-153099]
- Ticino Foundation for Cancer Research
- Virginia Boeger Foundation
- Fidinam
- Ceresio Foundation
- Novartis Foundation
- Ticino Foundation for Cancer Research (Mario Luvini fellowship)
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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.
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