<i>MYCNOS</i> functions as an antisense RNA regulating <i>MYCN</i>

<div><p>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 (<i>MYCNOS</i>) 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 <i>MYCNOS</i> transcripts function as a modulator of the <i>MYCN</i> locus, affecting <i>MYCN</i> promoter usage and recruiting various proteins, including the Ras GTPase-activating protein-binding protein G3BP1, to the upstream <i>MYCN</i> promoter. Overexpression of <i>MYCNOS</i> results in a reduction of upstream <i>MYCN</i> promoter usage and increased MYCN expression, suggesting that the protein-coding <i>MYCNOS</i> also functions as a regulator of <i>MYCN</i> ultimately controlling <i>MYCN</i> transcriptional variants. The observations presented here demonstrate that protein-coding transcripts can regulate gene transcription and can tether regulatory proteins to target loci.</p></div>