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Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress‐dependent mRNAs
Authors:
Manuel
Martín‐expósito
(Instituto de Biomedicina de Valencia (CSIC); Centro de Investigación Príncipe Felipe (CIPF))
,
Maria‐eugenia
Gas
(Centro de Investigación Príncipe Felipe (CIPF))
,
Nada
Mohamad
(Instituto de Biomedicina de Valencia (CSIC))
,
Carme
Nuño‐cabanes
(Instituto de Biomedicina de Valencia (CSIC); Centro de Investigación Príncipe Felipe (CIPF))
,
Ana
Tejada‐colón
(Instituto de Biomedicina de Valencia (CSIC))
,
Pau
Pascual‐garcía
(Centro de Investigación Príncipe Felipe (CIPF))
,
Lorena
De La Fuente
(Centro de Investigación Príncipe Felipe (CIPF))
,
Belén
Chaves‐arquero
(Institute of Physical‐Chemistry “Rocasolano” (CSIC))
,
Jonathan
Merran
(Johns Hopkins University School of Medicine)
,
Jeffry
Corden
(Johns Hopkins University School of Medicine)
,
Ana
Conesa
(University of Florida)
,
José Manuel
Pérez‐cañadillas
(Institute of Physical‐Chemistry “Rocasolano” (CSIC))
,
Jeronimo
Bravo
(Instituto de Biomedicina de Valencia (CSIC))
,
Susana
Rodríguez‐navarro
(Instituto de Biomedicina de Valencia (CSIC); Centro de Investigación Príncipe Felipe (CIPF))
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Embo Reports
, VOL 20
State:
Published (Approved)
Published:
October 2019
Diamond Proposal Number(s):
10121
Abstract: RNA‐binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four‐RNA recognition motif (RRM)‐containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6‐RRM4 directly interacts with the ubiquitin‐associated (UBA) domain of Mex67 through a loop containing tryptophan 442. Mip6 shuttles between the nucleus and the cytoplasm in a Mex67‐dependent manner and concentrates in cytoplasmic foci under stress. Photoactivatable ribonucleoside‐enhanced crosslinking and immunoprecipitation experiments show preferential binding of Mip6 to mRNAs regulated by the stress‐response Msn2/4 transcription factors. Consistent with this binding, MIP6 deletion affects their export and expression levels. Additionally, Mip6 interacts physically and/or functionally with proteins with a role in mRNA metabolism and transcription such as Rrp6, Xrn1, Sgf73, and Rpb1. These results reveal a novel role for Mip6 in the homeostasis of Msn2/4‐dependent transcripts through its direct interaction with the Mex67 UBA domain.
Journal Keywords: Mex67; Mip6; mRNA export; Msn2/4; RNA‐binding protein
Subject Areas:
Biology and Bio-materials
Instruments:
I04-Macromolecular Crystallography