HuD is a neural enhancer of global translation acting on mTORC1-responsive genes and sponged by the Y3 small non-coding RNA

Zuccotti, P.; Tebaldi, T.; Peroni, D.; Köhn, M.; Gasperini, L.; Potrich, V.; Dudnakova, T.; Sanguinetti, G.; Conti, L.; Macchi, P.; Tollervey, D.; Hüttelmaier, S.; Quattrone, A.

doi:10.1101/205658

bioRxiv · 10.1101/205658

HuD is a neural enhancer of global translation acting on mTORC1-responsive genes and sponged by the Y3 small non-coding RNA

Zuccotti, P.·Tebaldi, T.·Peroni, D.·Köhn, M.·Gasperini, L.·Potrich, V.·Dudnakova, T.·Sanguinetti, G.·Conti, L.·Macchi, P.·Tollervey, D.·Hüttelmaier, S.·Quattrone, A.

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Abstract

The RNA-binding protein HuD promotes neurogenesis and favors recovery from peripheral axon injury. HuD interacts with many mRNAs, altering both stability and translation efficiency. UV-crosslinking and analysis of cDNA (CRAC) generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells. HuD target sites were identified in 1304 mRNAs, predominantly in the 3UTR, with enrichment for genes involved in protein synthesis and axonogenesis. HuD bound many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlated with the translational efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target was the abundant, small non-coding RNA Y3, which represented 70% of HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its activity. These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/205658_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (69K):\norg.highwire.dtl.DTLVardef@17b2d21org.highwire.dtl.DTLVardef@1cfdc8borg.highwire.dtl.DTLVardef@1984f88org.highwire.dtl.DTLVardef@8da1ee_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zuccotti, P., Tebaldi, T., Peroni, D., Köhn, M., Gasperini, L., Potrich, V., Dudnakova, T., Sanguinetti, G., Conti, L., Macchi, P., Tollervey, D., Hüttelmaier, S., Quattrone, A.. 2017-10-19. HuD is a neural enhancer of global translation acting on mTORC1-responsive genes and sponged by the Y3 small non-coding RNA. https://doi.org/10.1101/205658

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