Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes
Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes
Summary RNA transport and local translation provide spatial control of gene expression, and RNA binding proteins (RBPs) act as critical adapters in this multi-step process. Muscleblind-like (MBNL) RNA binding proteins, implicated in myotonic dystrophy and cancer, localize RNAs to myoblast membranes and distal neurites through unknown mechanisms. We found that MBNL forms motile and anchored granules in neurons and myoblasts, and selectively associates with kinesins Kif1bα and Kif1c through its zinc finger (ZnF) domains. Other RBPs with similar ZnFs also associate with these kinesins, implicating a motor-RBP specificity code. Live cell imaging and fractionation revealed that membrane anchoring is mediated through the unstructured carboxy-terminal tail of MBNL1. Both kinesin- and membrane-recruitment functions were reconstituted using MBNL-MS2 coat protein fusions. This approach, termed RBP Module Recruitment and Imaging (RBP-MRI), decouples RNA binding, kinesin recruitment, and membrane anchoring functions, while also establishing general strategies for studying multi-functional, modular domains of RBPs.
Bassell Gary J.、Hildebrandt Ryan P.、Janusz-Kaminska Aleksandra、Denes Lance T.、Boggupalli Devi Prasad、Li Zhuangyue、Knudson Luke A.、Saxena Tanvi、Wang Eric T.、Moss Kathryn R.、Lin Kun
Department of Cell Biology, Emory University School of MedicineDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of FloridaDepartment of Cell Biology, Emory University School of MedicineDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of FloridaDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of FloridaDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of FloridaDepartment of Cell Biology, Emory University School of MedicineDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of FloridaDepartment of Molecular Genetics & Microbiology, Center for Neurogenetics, Genetics Institute, University of Florida||Myology Institute, University of FloridaDepartment of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of Medicine
分子生物学细胞生物学遗传学
Bassell Gary J.,Hildebrandt Ryan P.,Janusz-Kaminska Aleksandra,Denes Lance T.,Boggupalli Devi Prasad,Li Zhuangyue,Knudson Luke A.,Saxena Tanvi,Wang Eric T.,Moss Kathryn R.,Lin Kun.Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes[EB/OL].(2025-03-28)[2025-07-22].https://www.biorxiv.org/content/10.1101/2022.07.06.498900.点此复制
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