PT  - JOURNAL ARTICLE
AU  - Caryn R. Hale
AU  - Kirsty Sawicka
AU  - Kevin Mora
AU  - John Fak
AU  - Jin Joo Kang
AU  - Paula Cutrim
AU  - Katarzyna Cialowicz
AU  - Thomas Carroll
AU  - Robert B. Darnell
TI  - FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons
AID  - 10.1101/2021.07.18.452839
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.18.452839
4099  - http://biorxiv.org/content/early/2021/07/19/2021.07.18.452839.short
4100  - http://biorxiv.org/content/early/2021/07/19/2021.07.18.452839.full
AB  - Neurons are believed to rely on dendritic localization and translation of mRNAs in order to generate activity-dependent changes in the synaptic plasticity. Here, we develop a strategy combining compartment-specific CLIP and TRAP in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. This revealed transcripts that have differentially localized alternative 3’UTR and splicing isoforms. FMRP targets are overrepresented among dendritic mRNAs, and compartment-specific FMRP-CLIP defined 383 dendritic FMRP targets, and also allowed for segregation of whole-cell FMRP targets into functional modules that are locally regulated by FMRP. In the absence of FMRP, dendritic FMRP targets show increased ribosome association, consistent with reported roles for FMRP in translational repression. Together, the data support a model in which distinct patterns of FMRP localization allow it to differentially regulate the expression of nuclear proteins and synaptic proteins within different compartments of a single neuronal cell type.Competing Interest StatementThe authors have declared no competing interest.