Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Endosomes / genetics
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Endosomes / metabolism
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Membrane Transport Proteins / metabolism
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Oligopeptides
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RNA / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Toll-Like Receptor 2 / agonists
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Toll-Like Receptor 9 / agonists
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Ustilago* / genetics
Substances
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Fungal Proteins
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Membrane Transport Proteins
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Oligopeptides
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RNA, Messenger
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RNA-Binding Proteins
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Toll-Like Receptor 2
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Toll-Like Receptor 9
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RNA
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PAM2-CSK4
Grants and funding
The work was funded by grants from the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy EXC-2048/1 - Project ID 39068111 to MF; Project-ID 267205415 – SFB 1208 to MF (project A09), HG (project A03), and LS (project A01). The Center for Structural Studies was funded by the Deutsche Forschungsgemeinschaft (DFG Grant number 417919780; INST 208/740-1 FUGG; INST 208/761-1 FUGG to S.H.J S). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.