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

Sara Napoli, Valentina Piccinelli, Sarah N Mapelli, Giuseppina Pisignano, Carlo V Catapano

Research output: Contribution to journalArticlepeer-review

13 Citations (SciVal)


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 languageEnglish
Pages (from-to)1742-1755
Number of pages14
JournalRNA Biology
Issue number12
Early online date11 Oct 2017
Publication statusPublished - 2 Dec 2017


  • 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


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