A MademoiseLLE domain binding platform links the key RNA transporter to endosomes.

Senthil-Kumar Devan, Stephan Schott-Verdugo, Kira Müntjes, Lilli Bismar, Jens Reiners, Eymen Hachani, Lutz Schmitt, Astrid Höppner, Sander Hj Smits, Holger Gohlke, Michael Feldbrügge

PLoS genetics 2022 Jun

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Spatiotemporal expression can be achieved by transport and translation of mRNAs at defined subcellular sites. An emerging mechanism mediating mRNA trafficking is microtubule-dependent co-transport on shuttling endosomes. Although progress has been made in identifying various components of the endosomal mRNA transport machinery, a mechanistic understanding of how these RNA-binding proteins are connected to endosomes is still lacking. Here, we demonstrate that a flexible MademoiseLLE (MLLE) domain platform within RNA-binding protein Rrm4 of Ustilago maydis is crucial for endosomal attachment. Our structure/function analysis uncovered three MLLE domains at the C-terminus of Rrm4 with a functionally defined hierarchy. MLLE3 recognises two PAM2-like sequences of the adaptor protein Upa1 and is essential for endosomal shuttling of Rrm4. MLLE1 and MLLE2 are most likely accessory domains exhibiting a variable binding mode for interaction with currently unknown partners. Thus, endosomal attachment of the mRNA transporter is orchestrated by a sophisticated MLLE domain binding platform.

Citation

Senthil-Kumar Devan, Stephan Schott-Verdugo, Kira Müntjes, Lilli Bismar, Jens Reiners, Eymen Hachani, Lutz Schmitt, Astrid Höppner, Sander Hj Smits, Holger Gohlke, Michael Feldbrügge. A MademoiseLLE domain binding platform links the key RNA transporter to endosomes. PLoS genetics. 2022 Jun;18(6):e1010269