التفاصيل البيبلوغرافية
| العنوان: |
The Intrinsically Disordered C-Terminal Domain Triggers Nucleolar Localization and Function Switch of PARN in Response to DNA Damage |
| المؤلفون: |
Tian-Li Duan, Guang-Jun He, Li-Dan Hu, Yong-Bin Yan |
| المصدر: |
Cells, Vol 8, Iss 8, p 836 (2019) |
| بيانات النشر: |
MDPI AG, 2019. |
| سنة النشر: |
2019 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
DNA damage response, function switch, intrinsically disordered domain, nucleolar localization, phosphorylation, poly(A)-specific ribonuclease (PARN), RNA maturation, structure switch, Cytology, QH573-671 |
| الوصف: |
Poly(A)-specific ribonuclease (PARN), a multifunctional multi-domain deadenylase, is crucial to the regulation of mRNA turnover and the maturation of various non-coding RNAs. Despite extensive studies of the well-folding domains responsible for PARN catalysis, the structure and function of the C-terminal domain (CTD) remains elusive. PARN is a cytoplasm−nucleus shuttle protein with concentrated nucleolar distribution. Here, we identify the nuclear and nucleolar localization signals in the CTD of PARN. Spectroscopic studies indicated that PARN-CTD is intrinsically disordered with loosely packed local structures/tertiary structure. Phosphorylation-mimic mutation S557D disrupted the local structure and facilitated the binding of the CTD with the well-folded domains, with no impact on PARN deadenylase activity. Under normal conditions, the nucleolus-residing PARN recruited CBP80 into the nucleoli to repress its deadenylase activity, while DNA damage-induced phosphorylation of PARN-S557 expelled CBP80 from the nucleoli to discharge activity inhibition and attracted nucleoplasm-located CstF-50 into the nucleoli to activate deadenylation. The structure switch-induced function switch of PARN reshaped the profile of small nuclear non-coding RNAs to respond to DNA damage. Our findings highlight that the structure switch of the CTD induced by posttranslational modifications redefines the subset of binding partners, and thereby the RNA targets in the nucleoli. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/8/8/836; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells8080836 |
| URL الوصول: |
https://doaj.org/article/3bd25ee7e67c46058e7361cbd03c299c |
| رقم الانضمام: |
edsdoj.3bd25ee7e67c46058e7361cbd03c299c |
| قاعدة البيانات: |
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