title: The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3'-End Processing Following UV-Induced DNA Damage.
abstract: Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage response leading to a profound impact on the level of protein expression since unprocessed transcripts at the 3'-end will be degraded or unable to be transported to the cytoplasm. However, a compensatory mechanism involving the binding of the hnRNP H/F family of RNA binding proteins to an RNA G-quadruplex (G4) structure located in the vicinity of a polyadenylation site has previously been described to allow the transcript encoding the p53 tumour suppressor protein to be properly processed during DNA damage and to provide the cells with a way to react to DNA damage. Here we report that the DEAH (Asp-Glu-Ala-His) box RNA helicase DHX36/RHAU/G4R1, which specifically binds to and resolves parallel-stranded G4, is necessary to maintain p53 pre-mRNA 3'-end processing following UV-induced DNA damage. DHX36 binds to the p53 RNA G4, while mutation of the G4 impairs the ability of DHX36 to maintain pre-mRNA 3'-end processing. Stabilization of the p53 RNA G4 with two different G4 ligands (PNADOTASQ and PhenDC3), which is expected from previous studies to prevent DHX36 from binding and unwinding G4s, also impairs p53 pre-mRNA 3'-end processing following UV. Our work identifies DHX36 as a new actor in the compensatory mechanisms that are in place to ensure that the mRNAs encoding p53 are still processed following UV.
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France; Equipe Labellisée Ligue Contre le Cancer, F-91405 Orsay, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Newman
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France; Equipe Labellisée Ligue Contre le Cancer, F-91405 Orsay, France.
authors.forename: Rym
authors.initials: R
authors.lastname: Sfaxi
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR9187-INSERM U1196, F-91405 Orsay, France; Université Paris Sud, Université Paris-Saclay, UMR9187-INSERM U1196, F-91405 Orsay, France.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Saha
authors.affiliation: Institute of Molecular Chemistry, University of Dijon, ICMUB CNRS UMR6302, F-21078 Dijon, France.
authors.forename: David
authors.initials: D
authors.lastname: Monchaud
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR9187-INSERM U1196, F-91405 Orsay, France; Université Paris Sud, Université Paris-Saclay, UMR9187-INSERM U1196, F-91405 Orsay, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France; Equipe Labellisée Ligue Contre le Cancer, F-91405 Orsay, France. Electronic address: stephan.vagner@curie.fr.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Vagner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000072283:A549 Cells; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D054856:G-Quadruplexes; D045325:HCT116 Cells; D006801:Humans; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D020413:3' Untranslated Regions; D012322:RNA Precursors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C466988:DHX36 protein, human; D053487:DEAD-box RNA Helicases
keywords: G-quadruplex ligand; RNA binding proteins; genome stability; polyadenylation; post-transcriptional gene regulation