التفاصيل البيبلوغرافية
| العنوان: |
The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3′-End Processing Following UV-Induced DNA Damage. |
| المؤلفون: |
Newman, Michelle1,2,3, Sfaxi, Rym1,2,3, Saha, Abhijit4,5, Monchaud, David6, Teulade-Fichou, Marie-Paule4,5, Vagner, Stéphan1,2,3 stephan.vagner@curie.fr |
| المصدر: |
Journal of Molecular Biology. Oct2017, Vol. 429 Issue 21, p3121-3131. 11p. |
| مصطلحات موضوعية: |
*RNA helicase, *QUADRUPLEX nucleic acids, *MESSENGER RNA, *DNA damage, *RNA-binding proteins |
| مستخلص: |
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 ( PNA DOTASQ 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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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