Analysis of NRAS RNA G-quadruplex binding proteins reveals DDX3X as a novel interactor of cellular G-quadruplex containing transcripts

Herdy, B., Mayer, C., Varshney, D., Marsico, G., Murat, P., Taylor, C., D'Santos, C., Tannahill, D. & Balasubramanian, S., 30-Nov-2018, In : Nucleic Acids Research. 46, 21, p. 11592-11604 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Barbara Herdy
  • Clemens Mayer
  • Dhaval Varshney
  • Giovanni Marsico
  • Pierre Murat
  • Chris Taylor
  • Clive D'Santos
  • David Tannahill
  • Shankar Balasubramanian

RNA G-quadruplexes (rG4s) are secondary structures in mRNAs known to influence RNA post-transcriptional mechanisms thereby impacting neurodegenerative disease and cancer. A detailed knowledge of rG4-protein interactions is vital to understand rG4 function. Herein, we describe a systematic affinity proteomics approach that identified 80 high-confidence interactors that assemble on the rG4 located in the 5'-untranslated region (UTR) of the NRAS oncogene. Novel rG4 interactors included DDX3X, DDX5, DDX17, GRSF1 and NSUN5. The majority of identified proteins contained a glycine-arginine (GAR) domain and notably GAR-domain mutation in DDX3X and DDX17 abrogated rG4 binding. Identification of DDX3X targets by transcriptome-wide individual-nucleotide resolution UV-crosslinking and affinity enrichment (iCLAE) revealed a striking association with 5'-UTR rG4-containing transcripts which was reduced upon GAR-domain mutation. Our work highlights hitherto unrecognized features of rG4 structure-protein interactions that highlight new roles of rG4 structures in mRNA post-transcriptional control.

Original languageEnglish
Pages (from-to)11592-11604
Number of pages13
JournalNucleic Acids Research
Issue number21
Publication statusPublished - 30-Nov-2018



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