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

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Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs.
EMBO Reports ( IF 6.5 ) Pub Date : 2019-11-03 , DOI: 10.15252/embr.201947964
Manuel Martín-Expósito _{1,

2} , Maria-Eugenia Gas ₂ , Nada Mohamad ₃ , Carme Nuño-Cabanes _{1,

2} , Ana Tejada-Colón ₁ , Pau Pascual-García ₂ , Lorena de la Fuente ₄ , Belén Chaves-Arquero ₅ , Jonathan Merran ₆ , Jeffry Corden ₆ , Ana Conesa _{7,

8} , José Manuel Pérez-Cañadillas ₅ , Jerónimo Bravo ₃ , Susana Rodríguez-Navarro _{1,

2}

Affiliation

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.

中文翻译：

Mip6 直接与 Mex67 UBA 结构域结合，以维持低水平的 Msn2/4 应激依赖性 mRNA。

RNA 结合蛋白 (RBP) 参与基因表达的所有步骤，强调了它们作为 RNA 稳态调节剂的潜力。我们从结构和功能上表征了 Mip6（一种包含四 RNA 识别基序 (RRM) 的 RBP），作为输出因子 Mex67 的功能和物理相互作用因子。 Mip6-RRM4 通过含有色氨酸 442 的环直接与 Mex67 的泛素相关 (UBA) 结构域相互作用。Mip6 以 Mex67 依赖性方式在细胞核和细胞质之间穿梭，并在应激下集中在细胞质灶中。光活化核糖核苷增强交联和免疫沉淀实验表明，Mip6 优先结合受应激反应 Msn2/4 转录因子调节的 mRNA。与这种结合一致，MIP6 缺失会影响它们的输出和表达水平。此外，Mip6 在物理和/或功能上与在 mRNA 代谢和转录中发挥作用的蛋白质（例如 Rrp6、Xrn1、Sgf73 和 Rpb1）相互作用。这些结果揭示了 Mip6 通过与 Mex67 UBA 结构域直接相互作用，在 Msn2/4 依赖性转录本的稳态中发挥新作用。

更新日期：2019-12-05

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