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

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This publication doesn't include Faculty of Medicine. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.

Authors

YADAV Deepak Kumar ZIGÁČKOVÁ Dagmar ZLOBINA Maria KLUMPLER Tomáš BEAUMONT Christelle KUBÍČKOVÁ Monika VAŇÁČOVÁ Štěpánka LUKAVSKY Peter

Year of publication 2020
Type Article in Periodical
Magazine / Source Nucleic acids research
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://watermark.silverchair.com/gkz1163.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAArMwggKvBgkqhkiG9w0BBwagggKgMIICnAIBADCCApUGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM93m65EaHAul9lvZ3AgEQgIICZgl4kN1MOxCY84aEvwwQEi6vjxrtsNYzBuhYRTUjwbqxdd
Doi http://dx.doi.org/10.1093/nar/gkz1163
Keywords DOUBLE-STRANDED-RNA; NMR STRUCTURE DETERMINATION; LARGE-SCALE PREPARATION; BICOID MESSENGER-RNA; SECONDARY STRUCTURES; BINDING PROTEIN; DOMAIN; PURIFICATION; NOESY; LOCALIZATION
Description 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 factorl (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 alpha 1, the beta 1-beta 2 loop anchors the dsRBD at the end of the dsRNA and lysines in helix alpha 2 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.
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