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Staufen1 reads out structure and sequence features in ARF1 dsRNA for target recognition

DOI: 10.1093/nar/gkz1163 DOI Help

Authors: Deepak Kumar Yadav (Central European Institute of Technology, Masaryk University) , Dagmar Zigáčková (Central European Institute of Technology, Masaryk University) , Maria Zlobina (Central European Institute of Technology, Masaryk University) , Tomas Klumpler (Central European Institute of Technology, Masaryk University) , Christelle Beaumont (Central European Institute of Technology, Masaryk University) , Monika Kubíčková (Central European Institute of Technology, Masaryk University) , Štěpánka Vaňáčová (Central European Institute of Technology, Masaryk University) , Peter J. Lukavsky (Central European Institute of Technology, Masaryk University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research , VOL 37

State: Published (Approved)
Published: December 2019
Diamond Proposal Number(s): 21035

Open Access Open Access

Abstract: Staufen1 (STAU1) is a dsRNA binding protein mediating mRNA transport and localization, translational control and STAU1-mediated mRNA decay (SMD). The STAU1 binding site (SBS) within human ADP-ribosylation factor1 (ARF1) 3′UTR binds STAU1 and this downregulates ARF1 cytoplasmic mRNA levels by SMD. However, how STAU1 recognizes specific mRNA targets is still under debate. Our structure of the ARF1 SBS–STAU1 complex uncovers target recognition by STAU1. STAU1 dsRNA binding domain (dsRBD) 4 interacts with two pyrimidines and one purine from the minor groove side via helix α1, the β1–β2 loop anchors the dsRBD at the end of the dsRNA and lysines in helix α2 bind to the phosphodiester backbone from the major groove side. STAU1 dsRBD3 displays the same binding mode with specific recognition of one guanine base. Mutants disrupting minor groove recognition of ARF1 SBS affect in vitro binding and reduce SMD in vivo. Our data thus reveal how STAU1 recognizes minor groove features in dsRNA relevant for target selection.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 09/01/2020 10:25

Documents:
g545gghb.pdf

Discipline Tags:

Life Sciences & Biotech Genetics Structural biology Chemistry Biochemistry

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)