Year: 2018
Type: article
Abstract: mRNA translation in axons enables neurons to introduce new proteins at sites distant from their cell body.mRNAprotein interactions drive this post-transcriptional regulation, yet knowledge of RNA binding proteins (RBP) in axons is limited.Here we used proteomics to identify RBPs interacting with the axonal localizing motifs of Nrn1, Hmgb1, Actb, and Gap43 mRNAs, revealing many novel RBPs in axons.Interestingly, no RBP is shared between all four RNA motifs, suggesting graded and overlapping specificities of RBP-mRNA pairings.A systematic assessment of axonal mRNAs interacting with hnRNP H1, hnRNP F, and hnRNP K, proteins that bound with high specificity to Nrn1 and Hmgb1, revealed that axonal mRNAs segregate into axon growth-associated RNA regulons based on hnRNP interactions.Axotomy increases axonal transport of hnRNPs H1, F, and K, depletion of these hnRNPs decreases axon growth and reduces axonal mRNA levels and axonal protein synthesis.Thus, subcellular hnRNPinteracting RNA regulons support neuronal growth and regeneration.
Source: Molecular & Cellular Proteomics
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: Howard Hughes Medical Institute, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, University of South Carolina, Weizmann Institute of Science, National Institutes of Health, University of California, San Francisco, Office of the Vice President for Research, University of South Carolina, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G3150505413, Center for Targeted Therapeutics, Functional identification of new mechanisms of neurotoxicity induced by HIV and drugs of abuse, Bio-Organic Biomedical Mass Spectrometry Resource, G758631956, Modifying intrinsic growth capacity through axonal mRNA translation, Destabilization of axonal mRNAs by KHSRP complexes during axon regeneration
OpenAlex ID: W2883303049