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.
Original language | English |
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Pages (from-to) | 1742-1755 |
Number of pages | 14 |
Journal | RNA Biology |
Volume | 14 |
Issue number | 12 |
Early online date | 11 Oct 2017 |
DOIs | |
Publication status | Published - 2 Dec 2017 |
Keywords
- 3' Untranslated Regions
- Acetylation
- Cell Line, Tumor
- Cloning, Molecular
- Epigenesis, Genetic
- Gene Expression Regulation
- Genes, myc
- Genetic Loci
- Histones/metabolism
- Humans
- Models, Biological
- Nucleic Acid Conformation
- RNA, Antisense/genetics
- RNA, Untranslated/genetics
- Ribonuclease III/metabolism
- Transcription Initiation Site
- Transcription, Genetic