hnRNPs Interacting with mRNA Localization Motifs Define Axonal RNA Regulons

Seung Joon Lee, Juan A. Oses-Prieto, Riki Kawaguchi, Pabitra K. Sahoo, Amar N. Kar, Meir Rozenbaum, David Oliver, Shreya Chand, Hao Ji, Michael Shtutman, Sharmina Miller-Randolph, Ross J. Taylor, Mike Fainzilber, Giovanni Coppola, Alma L. Burlingame, Jeffery L. Twiss

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2091-2106
Number of pages16
JournalMolecular & Cellular Proteomics
Issue number11
Early online date23 Jul 2018
StatePublished - 1 Nov 2018

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology


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