TY - JOUR
T1 - hnRNPs Interacting with mRNA Localization Motifs Define Axonal RNA Regulons
AU - Lee, Seung Joon
AU - Oses-Prieto, Juan A.
AU - Kawaguchi, Riki
AU - Sahoo, Pabitra K.
AU - Kar, Amar N.
AU - Rozenbaum, Meir
AU - Oliver, David
AU - Chand, Shreya
AU - Ji, Hao
AU - Shtutman, Michael
AU - Miller-Randolph, Sharmina
AU - Taylor, Ross J.
AU - Fainzilber, Mike
AU - Coppola, Giovanni
AU - Burlingame, Alma L.
AU - Twiss, Jeffery L.
N1 - The authors thank Jill Turner, Sofia Lizarraga, Fabienne Poulain, and Deanna S. Smith for constructive comments and guidance. MS experiments were performed at the Biomedical Mass Spectrometry Resource at UCSF supported by funding from the Howard Hughes Medical Institute (to ALB). JLT is the Endowed SmartState Chair in Childhood Neurotherapeutics at the Univ. South Carolina. MF is the incumbent of the Chaya Professorial Chair in Molecular Neuroscience at the Weizmann Institute of Science. HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) http://dx.doi.org/10.13039/100000065R01-NS045196R01-NS089633HHS | NIH | National Institute of General Medical Sciences (NIGMS) http://dx.doi.org/10.13039/1000000578P41-GM1034811P20GM109091–01HHS | NIH | National Institute on Drug Abuse (NIDA) http://dx.doi.org/10.13039/100000026R03-DA043428–01A1Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF) http://dx.doi.org/10.13039/100005984NAUSC | Office of the Vice President for Research, University of South Carolina http://dx.doi.org/10.13039/100010557ASPIRE. Author contributions: S.J.L., A.N.K., and J.L.T. designed research; S.J.L., J.A.O.-P., R.K., P.K.S., A.N.K., M.R., S.C., S.M.-R., and R.J.T. performed research; S.J.L., J.A.O.-P., R.K., P.K.S., D.O., S.C., H.J., M.S., M.F., G.C., A.L.B., and J.L.T. analyzed data; S.J.L., R.K., and J.L.T. wrote the paper; J.A.O.-P., R.K., M.R., D.O., M.S., M.F., G.C., and A.L.B. contributed new reagents/analytic tools. This work was supported by grants from NIH (R01-NS041596 to JLT, 8P41-GM103481 to ALB, 1P20GM109091-01 to MS, R03-DA043428-01A1 to MS), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to ALB, GC, MF and JLT) and ASPIRE grant from the Office of the Vice President for Research at the University of South Carolina (to SJL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding sources.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
U2 - 10.1074/mcp.RA118.000603
DO - 10.1074/mcp.RA118.000603
M3 - مقالة
C2 - 30038033
SN - 1535-9476
VL - 17
SP - 2091
EP - 2106
JO - Molecular & Cellular Proteomics
JF - Molecular & Cellular Proteomics
IS - 11
ER -