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

Toma Tebaldi; Paola  Zuccotti; Daniele Peroni; Marcel Köhn; Lisa Gasperini; Valentina  Potrich; Veronica Bonazza; Tatiana Dudnakova; Annalisa Rossi; Guido Sanguinetti; Luciano Conti; Paolo Macchi; Vito D'Agostino; Gabriella  Viero; David Tollervey; Stefan Hüttelmaier; Alessandro  Quattrone

doi:10.1016/j.molcel.2018.06.032

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

Toma Tebaldi, Paola Zuccotti, Daniele Peroni, Marcel Köhn, Lisa Gasperini, Valentina Potrich, Veronica Bonazza, Tatiana Dudnakova, Annalisa Rossi, Guido Sanguinetti, Luciano Conti, Paolo Macchi, Vito D'Agostino, Gabriella Viero, David Tollervey, Stefan Hüttelmaier, Alessandro Quattrone

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1304 mRNAs, almost exclusively in the 3'UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. 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.

Original language	English
Pages (from-to)	256-270
Number of pages	26
Journal	Molecular Cell
Volume	71
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2018.06.032
Publication status	Published - 19 Jul 2018

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10.1016/j.molcel.2018.06.032Licence: Creative Commons: Attribution (CC-BY)

MOLECULAR-CELL-D-17-01777_R3Accepted author manuscript, 15.9 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)
Tebaldi et al 2018Final published version, 4.6 MBLicence: CC BY

https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30507-0Licence: Creative Commons: Attribution (CC-BY)

Nuclear RNA processing and surveillance
Tollervey, D.
UK-based charities
1/10/16 → 30/09/26
Project: Research

Cite this

Tebaldi, T., Zuccotti, P., Peroni, D., Köhn, M., Gasperini, L., Potrich, V., Bonazza, V., Dudnakova, T., Rossi, A., Sanguinetti, G., Conti, L., Macchi, P., D'Agostino, V., Viero, G., Tollervey, D., Hüttelmaier, S., & Quattrone, A. (2018). HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA. Molecular Cell, 71(2), 256-270. https://doi.org/10.1016/j.molcel.2018.06.032

@article{b661bc79046c4ad3ab97de722906372a,

title = "HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA",

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. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1304 mRNAs, almost exclusively in the 3'UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. 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.",

author = "Toma Tebaldi and Paola Zuccotti and Daniele Peroni and Marcel K{\"o}hn and Lisa Gasperini and Valentina Potrich and Veronica Bonazza and Tatiana Dudnakova and Annalisa Rossi and Guido Sanguinetti and Luciano Conti and Paolo Macchi and Vito D'Agostino and Gabriella Viero and David Tollervey and Stefan H{\"u}ttelmaier and Alessandro Quattrone",

year = "2018",

month = jul,

day = "19",

doi = "10.1016/j.molcel.2018.06.032",

language = "English",

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pages = "256--270",

journal = "Molecular Cell",

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publisher = "Cell Press",

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Tebaldi, T, Zuccotti, P, Peroni, D, Köhn, M, Gasperini, L, Potrich, V, Bonazza, V, Dudnakova, T, Rossi, A, Sanguinetti, G, Conti, L, Macchi, P, D'Agostino, V, Viero, G, Tollervey, D, Hüttelmaier, S & Quattrone, A 2018, 'HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA', Molecular Cell, vol. 71, no. 2, pp. 256-270. https://doi.org/10.1016/j.molcel.2018.06.032

TY - JOUR

T1 - HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA

AU - Tebaldi, Toma

AU - Zuccotti, Paola

AU - Peroni, Daniele

AU - Köhn, Marcel

AU - Gasperini, Lisa

AU - Potrich, Valentina

AU - Bonazza, Veronica

AU - Dudnakova, Tatiana

AU - Rossi, Annalisa

AU - Sanguinetti, Guido

AU - Conti, Luciano

AU - Macchi, Paolo

AU - D'Agostino, Vito

AU - Viero, Gabriella

AU - Tollervey, David

AU - Hüttelmaier, Stefan

AU - Quattrone, Alessandro

PY - 2018/7/19

Y1 - 2018/7/19

N2 - 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. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1304 mRNAs, almost exclusively in the 3'UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. 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.

AB - 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. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1304 mRNAs, almost exclusively in the 3'UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. 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.

U2 - 10.1016/j.molcel.2018.06.032

DO - 10.1016/j.molcel.2018.06.032

M3 - Article

SN - 1097-2765

VL - 71

SP - 256

EP - 270

JO - Molecular Cell

JF - Molecular Cell

IS - 2

ER -

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

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Projects

Nuclear RNA processing and surveillance

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