Journal
RNA BIOLOGY
Volume 12, Issue 8, Pages 893-899Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2015.1063773
Keywords
Transcriptional regulation; bidirectional promoter; neuroblastoma; RNA; G3BP1; MAP4
Categories
Funding
- NIAID [R56 AI096861-01, PO1 AI099783-01]
- Australian Research Council [FT1300100572, CA151574-01, RO1 CA153124-01]
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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.
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