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| Status |
Public on Aug 25, 2014 |
| Title |
Temporally defined neocortical translation and polysome assembly is determined by the RNA-binding protein, Hu antigen R |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Cortex was dissected from WT and HuR cKO mouse pups at embryonic day 13 (E13) or the day of birth (P0).
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| Contributor(s) |
Hart RP, Rasin MR, Kraushar ML, Thompson K |
| Citation(s) |
25157170, 26245956 |
| |
| Submission date |
Sep 12, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
|
| Phone |
848-445-1783
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| Organization name |
Rutgers University
|
| Department |
Cell Biology & Neuroscience
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| Street address |
604 Allison Rd Rm B430
|
| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA219065 |
| SRA |
SRP029912 |
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