hnRNPs Interacting with mRNA Localization Motifs Define AxoNAl RNA Regulons

mRNA translation in axons eNAbles neurons to introduce new proteins at sites distant from their cell body. mRNA-protein 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...

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Bibliographic Details
Published inMolecular & cellular proteomics Vol. 17; no. 11; p. 2091
Main Authors Lee, Seung Joon, Oses-Prieto, Juan A, Kawaguchi, Riki, Sahoo, Pabitra K, Kar, Amar N, Rozenbaum, Meir, Oliver, David, Chand, Shreya, Ji, Hao, Shtutman, Michael, Miller-Randolph, SharmiNA, Taylor, Ross J, Fainzilber, Mike, Coppola, Giovanni, Burlingame, Alma L, Twiss, Jeffery L
Format Journal Article
LanguageEnglish
Published United States 01.11.2018
Subjects
hnRNP
axon growth
Neurobiology
RNA binding protein
Ribonucleoproteins
Subcellular aNAlysis
Bioinformatics
Affinity proteomics
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Summary:mRNA translation in axons eNAbles neurons to introduce new proteins at sites distant from their cell body. mRNA-protein 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 hnRNP-interacting RNA regulons support neuroNAl growth and regeneration.
ISSN:1535-9484