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

Manuel Martín-Expósito, Maria Eugenia Gas, Nada Mohamad, Carme Nuño-Cabanes, Ana Tejada-Colón, Pau Pascual-García, Lorena de la Fuente, Belén Chaves-Arquero, Jonathan Merran, Jeffry Corden, Ana Conesa, José Manuel Pérez-Cañadillas, Jerónimo Bravo, Susana Rodríguez-Navarro

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere47964
JournalEMBO Reports
Volume20
Issue number12
DOIs
StatePublished - Dec 5 2019

Keywords

  • Mex67
  • Mip6
  • Msn2/4
  • RNA-binding protein
  • mRNA export

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Martín-Expósito, M., Gas, M. E., Mohamad, N., Nuño-Cabanes, C., Tejada-Colón, A., Pascual-García, P., de la Fuente, L., Chaves-Arquero, B., Merran, J., Corden, J., Conesa, A., Pérez-Cañadillas, J. M., Bravo, J., & Rodríguez-Navarro, S. (2019). Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs. EMBO Reports, 20(12), [e47964]. https://doi.org/10.15252/embr.201947964