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| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Caryn R. Hale Kirsty Sawicka Kevin Mora John J. Fak Jin Joo Kang Paula Cutrim Katarzyna Cialowicz Thomas S. Carroll Robert B. Darnell |
| Abstract | Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity. Here, we develop a strategy combining compartment-specific crosslinking immunoprecipitation (CLIP) and translating ribosome affinity purification (TRAP) in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. We identify CA1 dendritic transcripts with differentially localized mRNA isoforms generated by alternative polyadenylation and alternative splicing, including many that have altered protein-coding capacity. Among dendritic mRNAs, FMRP targets were found to be overrepresented. Cell-type-specific FMRP-CLIP and TRAP in microdissected CA1 neuropil revealed 383 dendritic FMRP targets and suggests that FMRP differentially regulates functionally distinct modules in CA1 dendrites and cell bodies. FMRP regulates ~15–20% of mRNAs encoding synaptic functions and 10% of chromatin modulators, in the dendrite and cell body, respectively. In the absence of FMRP, dendritic FMRP targets had increased ribosome association, consistent with a function for FMRP in synaptic translational repression. Conversely, downregulation of FMRP targets involved in chromatin regulation in cell bodies suggests a role for FMRP in stabilizing mRNAs containing stalled ribosomes in this compartment. Together, the data support a model in which FMRP regulates the translation and expression of synaptic and nuclear proteins within different compartments of a single neuronal cell type. |
| e-ISSN | 2050084X |
| DOI | 10.7554/eLife.71892 |
| Journal | eLife |
| Volume Number | 10 |
| Language | English |
| Publisher | eLife Sciences Publications Ltd |
| Publisher Date | 2021-01-01 |
| Publisher Place | United Kingdom |
| Access Restriction | Open |
| Subject Keyword | Medicine Science Biology (general) Local Translation Fmrp Rna-binding Proteins Synaptic Plasticity Mrna Localization |
| Content Type | Text |
| Resource Type | Article |
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