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Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr

ABSTRACT: The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol and in axons of motoneurons, and that depletion of Ptbp2 affects axon growth. We identified Ptbp2 as a major interactor of the 3' UTR of Hnrnpr mRNA. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus, suggest a mechanism whereby Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD035196 | Pride | 2023-07-13

REPOSITORIES: Pride

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