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

YADAV, Deepak Kumar, Dagmar ZIGÁČKOVÁ, Maria ZLOBINA, Tomáš KLUMPLER, Christelle BEAUMONT, Monika KUBÍČKOVÁ, Štěpánka VAŇÁČOVÁ and Peter LUKAVSKY. Staufen1 reads out structure and sequence features in ARF1 dsRNA for target recognition. In FEBS Congress 2019. 2019. ISSN 2211-5463.

Basic information

• Original name: Staufen1 reads out structure and sequence features in ARF1 dsRNA for target recognition
• Authors: YADAV, Deepak Kumar (356 India, belonging to the institution), Dagmar ZIGÁČKOVÁ (203 Czech Republic, belonging to the institution), Maria ZLOBINA (643 Russian Federation, belonging to the institution), Tomáš KLUMPLER (203 Czech Republic, belonging to the institution), Christelle BEAUMONT (250 France, belonging to the institution), Monika KUBÍČKOVÁ (203 Czech Republic, belonging to the institution), Štěpánka VAŇÁČOVÁ (203 Czech Republic, belonging to the institution) and Peter LUKAVSKY (40 Austria, guarantor, belonging to the institution).
• Edition: FEBS Congress 2019, 2019.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.231
• RIV identification code: RIV/00216224:14740/19:00108212
• Organization unit: Central European Institute of Technology
• ISSN: 2211-5463
• UT WoS: 000486972400099
• Keywords in English: Staufen1; ARF1 dsRNA
• Tags: rivok
• Tags: International impact

Abstract

Most posttranscriptional regulation of gene expression is based on RNA elements in mRNAs recognized by RNA­binding proteins (RBPs). Besides primary sequence elements, a second layer of information is embedded in 3’UTRs of mRNAs in the form of RNA structure. Double­stranded RBPs (dsRBPs) can bind structures in 3’UTRs and then exert their function based on dsRNA target recognition through a combination of structure and sequence. Staufen1 (STAU1) is a dsRBP involved in mRNA transport and localization, translational control and mRNA decay by a STAU1­mediated mRNA decay (SMD) pathway. The STAU1 binding site (SBS) within human ADP­ribosylation factor1 (ARF1) 3’UTR is one such target and STAU1 binding to the SBS regulates ARF1 cytoplasmic mRNA levels by the SMD pathway. However, how STAU1 recognizes specific mRNA targets is still unknown. 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 alfa1, beta1­beta2 loop anchors the dsRBD at the end of the dsRNA and lysines in helix alfa2 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 reduce SMD in vivo but have minor effect on in vitro binding. Our data suggest how dsRNA recognition by STAU1 mediates diverse functions in gene expression pathways.

Links

• GA18-08153S, research and development project: Name: Molekulární podstata Staufen zprostředkované funkce 3'UTR

Investor: Czech Science Foundation