MYCN and helicases DDX17 and DDX5 have opposite effects on the production of readthrough-associated chimeric transcripts
Abstract
DEAD box helicases DDX17 and DDX5 control transcription termination and the associated processing of the 3' end of pre-messenger RNAs. Here, we demonstrate that the transcriptional readthrough induced by DDX17 depletion, either alone or in combination with DDX5, leads to an increased production of chimeric transcripts from tandemly oriented gene, or tracRNAs, in neuroblastoma cells. Analysis of neuroblastoma tumours in which tracRNAs are abundant revealed that low expression of DDX17 and DDX5 genes is associated with high-risk tumours and poor overall patient survival, and inversely linked with MYCN oncogene amplification. We demonstrate that changes in MYCN expression do not affect the expression of either helicase, but alter transcription termination leading to the production of tracRNAs. MYCN acts on termination through its direct binding to the 3' region of genes and it interacts with DDX17, suggesting that it may interfere with the activity of the helicase. Collectively, our work reveals a novel function of MYCN in transcription termination and suggests that the deregulation of MYCN and DDX17/DDX5 expression in neuroblastoma may lead to the expression of non-canonical and potentially harmful RNA molecules.
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BibTeX
@article{clerc2026mycn,
title = {{MYCN and helicases DDX17 and DDX5 have opposite effects on the production of readthrough-associated chimeric transcripts}},
author = {Valentine Clerc and Khouaila Aouadi and Jessica Valat and Xavier Grand and Lou-Sahra Khourab and Alizée Duquet and Nicolas Fontrodona and Matéo Bazire and Nicolas Rama and Didier Auboeuf and Benjamin Gibert and Franck Mortreux and Cyril F Bourgeois},
journal = {Cellular and Molecular Life Sciences},
year = {2026},
month = may,
doi = {10.1007/s00018-026-06254-6},
url = {https://cnrs.hal.science/hal-05732008v2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MYCN and helicases DDX17 and DDX5 have opposite effects on the production of readthrough-associated chimeric transcripts
AU - Valentine Clerc
AU - Khouaila Aouadi
AU - Jessica Valat
AU - Xavier Grand
AU - Lou-Sahra Khourab
AU - Alizée Duquet
AU - Nicolas Fontrodona
AU - Matéo Bazire
AU - Nicolas Rama
AU - Didier Auboeuf
AU - Benjamin Gibert
AU - Franck Mortreux
AU - Cyril F Bourgeois
PY - 2026
DA - 2026/05/28
JO - Cellular and Molecular Life Sciences
DO - 10.1007/s00018-026-06254-6
UR - https://cnrs.hal.science/hal-05732008v2
AB - DEAD box helicases DDX17 and DDX5 control transcription termination and the associated processing of the 3' end of pre-messenger RNAs. Here, we demonstrate that the transcriptional readthrough induced by DDX17 depletion, either alone or in combination with DDX5, leads to an increased production of chimeric transcripts from tandemly oriented gene, or tracRNAs, in neuroblastoma cells. Analysis of neuroblastoma tumours in which tracRNAs are abundant revealed that low expression of DDX17 and DDX5 genes is associated with high-risk tumours and poor overall patient survival, and inversely linked with MYCN oncogene amplification. We demonstrate that changes in MYCN expression do not affect the expression of either helicase, but alter transcription termination leading to the production of tracRNAs. MYCN acts on termination through its direct binding to the 3' region of genes and it interacts with DDX17, suggesting that it may interfere with the activity of the helicase. Collectively, our work reveals a novel function of MYCN in transcription termination and suggests that the deregulation of MYCN and DDX17/DDX5 expression in neuroblastoma may lead to the expression of non-canonical and potentially harmful RNA molecules.
SN - 1420-682X
SN - 1420-9071
ER -