Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs
Por:
M. MARTIN-EXPOSITO, M. GAS, N. MOHAMAD, C. NUNO-CABANES, A. TEJADA-COLON, P. PASCUAL-GARCIA, L. DE LA FUENTE, B. CHAVES-ARQUERO, J. MERRAN, J. CORDEN, A. CONESA, J. PEREZ-CANADILLAS, J. BRAVO and S. RODRIGUEZ-NAVARRO
Publicada:
3 nov 2019
Ahead of Print:
1 nov 2019
Resumen:
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.
Filiaciones:
M. MARTIN-EXPOSITO:
CSIC, Gene Express & RNA Metab Lab, Inst Biomed Valencia, Valencia, Spain
CIPF, Gene Express & RNA Metab Lab, Valencia, Spain
M. GAS:
CIPF, Gene Express & RNA Metab Lab, Valencia, Spain
N. MOHAMAD:
CSIC, Signal Transduct Lab, Inst Biomed Valencia, Valencia, Spain
:
CSIC, Gene Express & RNA Metab Lab, Inst Biomed Valencia, Valencia, Spain
CIPF, Gene Express & RNA Metab Lab, Valencia, Spain
A. TEJADA-COLON:
CSIC, Gene Express & RNA Metab Lab, Inst Biomed Valencia, Valencia, Spain
P. PASCUAL-GARCIA:
CIPF, Gene Express & RNA Metab Lab, Valencia, Spain
Univ Penn, Perelman Sch Med, Epigenet Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
:
CIPF, Genom Gene Express Lab, Valencia, Spain
B. CHAVES-ARQUERO:
CSIC, Dept Biol Phys Chem, Inst Phys Chem Rocasolano, Madrid, Spain
J. MERRAN:
Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
J. CORDEN:
Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
:
Univ Florida, Genet Inst, Gainesville, FL USA
Univ Florida, Microbiol & Cell Sci Dept, Inst Food & Agr Res, Gainesville, FL USA
J. PEREZ-CANADILLAS:
CSIC, Dept Biol Phys Chem, Inst Phys Chem Rocasolano, Madrid, Spain
J. BRAVO:
CSIC, Signal Transduct Lab, Inst Biomed Valencia, Valencia, Spain
:
CSIC, Gene Express & RNA Metab Lab, Inst Biomed Valencia, Valencia, Spain
CIPF, Gene Express & RNA Metab Lab, Valencia, Spain
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