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EMBO Rep ; 20(12): e47964, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31680439


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.

EMBO Rep ; 19(11)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30249596


Monoubiquitination of histone H2B (to H2Bub1) is required for downstream events including histone H3 methylation, transcription, and mRNA export. The mechanisms and players regulating these events have not yet been completely delineated. Here, we show that the conserved Ran-binding protein Mog1 is required to sustain normal levels of H2Bub1 and H3K4me3 in Saccharomyces cerevisiae Mog1 is needed for gene body recruitment of Rad6, Bre1, and Rtf1 that are involved in H2B ubiquitination and genetically interacts with these factors. We provide evidence that the absence of MOG1 impacts on cellular processes such as transcription, DNA replication, and mRNA export, which are linked to H2Bub1. Importantly, the mRNA export defect in mog1Δ strains is exacerbated by the absence of factors that decrease H2Bub1 levels. Consistent with a role in sustaining H2Bub and H3K4me3 levels, Mog1 co-precipitates with components that participate in these modifications such as Bre1, Rtf1, and the COMPASS-associated factors Shg1 and Sdc1. These results reveal a novel role for Mog1 in H2B ubiquitination, transcription, and mRNA biogenesis.

Histonas/metabolismo , RNA Polimerase II/genética , RNA Mensageiro/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteína ran de Ligação ao GTP/metabolismo , Imunoprecipitação da Cromatina , Repressão Epigenética , Regulação Fúngica da Expressão Gênica , Histonas/genética , RNA Polimerase II/metabolismo , Transporte de RNA , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteína de Ligação a TATA-Box/genética , Proteína de Ligação a TATA-Box/metabolismo , Transcrição Genética , Ubiquitinação , Proteína ran de Ligação ao GTP/genética
Curr Genet ; 64(3): 635-644, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29116388


Sus1 is a conserved protein involved in histone H2B de-ubiquitination and mRNA export from the nucleus in eukaryotes. Previous studies implicated Sus1 partners in genome integrity including telomere homeostasis. However, the implication of Sus1 in telomere maintenance remains largely unknown. In this study, we found that yeast Sus1 interacts physically and genetically with factors involved in telomere maintenance and its absence leads to elongated telomeres. Deletion of several of Sus1's partners also leads to longer telomeres. Our results rule out a direct role for Sus1 in recruiting telomerase subunits to telomeres. However, we observe that deletion of SUS1 leads to elongated telomeres even in the presence of mutations like sem1Δ, esc2Δ and rsc2Δ, which cause telomere shortening. We find that rsc2Δ (short telomeres) have reduced levels of mono-ubiquitinated histone H2B at lysine 123 (H2BK123ub1), whereas sus1Δ mutants or double-mutants sus1Δ rsc2Δ exhibit longer telomeres and higher H2BK123ub1 levels. These results suggest that Sus1 activity as a H2B de-ubiquitination modulator plays a role in negatively regulating telomere length. Our results provide solid evidence for a role of Sus1 in negatively regulating telomere length through the modulation of H2BK123 mono-ubiquitination and its interaction with the nuclear pore complex.

Cromossomos Fúngicos , Evolução Molecular , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Homeostase do Telômero , Replicação do DNA , Mutação , Telômero , Ubiquitinação