MYCNOS functions as an antisense RNA regulating MYCN

N Vadie, S Saayman, A Lenox, A Ackley, M Clemson… - RNA biology, 2015 - Taylor & Francis
N Vadie, S Saayman, A Lenox, A Ackley, M Clemson, J Burdach, J Hart, PK Vogt, KV Morris
RNA biology, 2015Taylor & Francis
Amplification or overexpression of neuronal MYC (MYCN) is associated with poor prognosis
of human neuroblastoma. Three isoforms of the MYCN protein have been described as well
as a protein encoded by an antisense transcript (MYCNOS) that originates from the opposite
strand at the MYCN locus. Recent findings suggest that some antisense long non-coding
RNAs (lncRNAs) can play a role in epigenetically regulating gene expression. Here we
report that MYCNOS transcripts function as a modulator of the MYCN locus, affecting MYCN …
Amplification or overexpression of neuronal MYC (MYCN) is associated with poor prognosis of human neuroblastoma. Three isoforms of the MYCN protein have been described as well as a protein encoded by an antisense transcript (MYCNOS) that originates from the opposite strand at the MYCN locus. Recent findings suggest that some antisense long non-coding RNAs (lncRNAs) can play a role in epigenetically regulating gene expression. Here we report that MYCNOS transcripts function as a modulator of the MYCN locus, affecting MYCN promoter usage and recruiting various proteins, including the Ras GTPase-activating protein-binding protein G3BP1, to the upstream MYCN promoter. Overexpression of MYCNOS results in a reduction of upstream MYCN promoter usage and increased MYCN expression, suggesting that the protein-coding MYCNOS also functions as a regulator of MYCN ultimately controlling MYCN transcriptional variants. The observations presented here demonstrate that protein-coding transcripts can regulate gene transcription and can tether regulatory proteins to target loci.
Taylor & Francis Online