Download MendeleyMip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs.
Martin-Exposito, M., Gas, M.E., Mohamad, N., Nuno-Cabanes, C., Tejada-Colon, A., Pascual-Garcia, P., de la Fuente, L., Chaves-Arquero, B., Merran, J., Corden, J., Conesa, A., Perez-Canadillas, J.M., Bravo, J., Rodriguez-Navarro, S.(2019) EMBO Rep : e47964-e47964
- PubMed: 31680439
- DOI: https://doi.org/10.15252/embr.201947964
- Primary Citation of Related Structures:
6EXZ - PubMed 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.
Organizational Affiliation:
Gene Expression and RNA Metabolism Laboratory, Instituto de Biomedicina de Valencia (CSIC), Valencia, Spain.
