Transcriptomics

Dataset Information

298

Temporally defined neocortical translation and polysome assembly is determined by the RNA-binding protein, Hu antigen R


ABSTRACT: Precise spatiotemporal control of mRNA translation machinery is essential to proper development of highly complex systems like the neocortex. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stagedependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of the initiation and elongation factors of the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some of the HuR-dependent proteins, the association with polysomes depends on the eIF2 alpha kinase 4 (eIF2ak4), which associated with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR prior to embryonic day 10 (E10) disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity. Cortex was dissected from mouse pups at embryonic day 13 (E13) or the day of birth (P0).

ORGANISM(S): Mus musculus  

SUBMITTER: Matthew L Kraushar   Kevin Thompson  Mladen-Roko Rasin  Ronald P. Hart  Ronald P Hart 

PROVIDER: E-GEOD-50809 | ArrayExpress | 2014-08-25

SECONDARY ACCESSION(S): SRP029912GSE50809PRJNA219065

REPOSITORIES: GEO, ArrayExpress, ENA

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Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R.

Kraushar Matthew L ML   Thompson Kevin K   Wijeratne H R Sagara HR   Viljetic Barbara B   Sakers Kristina K   Marson Justin W JW   Kontoyiannis Dimitris L DL   Buyske Steven S   Hart Ronald P RP   Rasin Mladen-Roko MR  

Proceedings of the National Academy of Sciences of the United States of America 20140825 36


Precise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphor  ...[more]

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