Gonatopoulos-Pournatzis et al. 2020 (PRJNA594022)

General Details

Title Autism-misregulated eIF4G microexons control synaptic translation and higher-order cognitive functions [Ribo-Seq]
Organism
Number of Samples 4
Release Date 2019/12/06 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP234998
ENA SRP234998
GEO GSE141599
BioProject PRJNA594022

Publication

Title
Authors Gonatopoulos-Pournatzis T, Niibori R, Salter EW, Weatheritt RJ, Tsang B, Farhangmehr S, Liang X, Braunschweig U, Roth J, Zhang S, Henderson T, Sharma E, Quesnel-Vallières M, Permanyer J, Maier S, Georgiou J, Irimia M, Sonenberg N, Forman-Kay JD, Gingras AC, Collingridge GL, Woodin MA, Cordes SP, Blencowe BJ
Journal Molecular cell
Publication Date 2020 Mar 19
Abstract Microexons represent the most highly conserved class of alternative splicing, yet their functions are poorly understood. Here, we focus on closely related neuronal microexons overlapping prion-like domains in the translation initiation factors, eIF4G1 and eIF4G3, the splicing of which is activity dependent and frequently disrupted in autism. CRISPR-Cas9 deletion of these microexons selectively upregulates synaptic proteins that control neuronal activity and plasticity and further triggers a gene expression program mirroring that of activated neurons. Mice lacking the Eif4g1 microexon display social behavior, learning, and memory deficits, accompanied by altered hippocampal synaptic plasticity. We provide evidence that the eIF4G microexons function as a translational brake by causing ribosome stalling, through their propensity to promote the coalescence of cytoplasmic granule components associated with translation repression, including the fragile X mental retardation protein FMRP. The results thus reveal an autism-disrupted mechanism by which alternative splicing specializes neuronal translation to control higher order cognitive functioning. Copyright © 2020 Elsevier Inc. All rights reserved.
PMC
PMID 31999954
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR10603614 PRJNA594022 Mus musculus CGR8 Ribo-Seq 0.0
SRR10603615 PRJNA594022 Mus musculus CGR8 Ribo-Seq 0.0
SRR10603616 PRJNA594022 Mus musculus CGR8 Ribo-Seq 0.0
SRR10603617 PRJNA594022 Mus musculus CGR8 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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