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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00108212" target="_blank" >RIV/00216224:14740/19:00108212 - isvavai.cz</a>

Result on the web

—

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA18-08153S" target="_blank" >GA18-08153S: Molecular basis of Staufen-mediated 3'UTR function</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů