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Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress‐dependent mRNAs

DOI: 10.15252/embr.201947964 DOI Help

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