Das et al. 2019 (PRJNA464051)

General Details

Title Widespread Alterations in Translation Elongation in the Brain of Fmr1 Knock-Out Mice
Organism
Number of Samples 14
Release Date 2018/05/04 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP144655
ENA SRP144655
GEO GSE114064
BioProject PRJNA464051

Publication

Title
Authors Das Sharma S,Metz JB,Li H,Hobson BD,Hornstein N,Sulzer D,Tang G,Sims PA
Journal Cell reports
Publication Date 2019 Mar 19
Abstract FMRP (fragile X mental retardation protein) is a polysome-associated RNA-binding protein encoded by Fmr1 that is lost in fragile X syndrome. Increasing evidence suggests that FMRP regulates both translation initiation and elongation, but the gene specificity of these effects is unclear. To elucidate the impact of Fmr1 loss on translation, we utilize ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in the cortex of 24-day-old Fmr1 knockout mice. We find a remarkably coherent reduction in ribosome footprint abundance per mRNA for previously identified, high-affinity mRNA binding partners of FMRP and an increase for terminal oligopyrimidine (TOP) motif-containing genes canonically controlled by mammalian target of rapamycin-eIF4E-binding protein-eIF4E binding protein-eukaryotic initiation factor 4E (mTOR-4E-BP-eIF4E) signaling. Amino acid motif- and gene-level analyses both show a widespread reduction of translational pausing in Fmr1 knockout mice. Our findings are consistent with a model of FMRP-mediated regulation of both translation initiation through eIF4E and elongation that is disrupted in fragile X syndrome. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
PMC PMC6457272
PMID 30893603
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR7124015 PRJNA464051 Mus musculus RNA-Seq
SRR7124016 PRJNA464051 Mus musculus RNA-Seq
SRR7124017 PRJNA464051 Mus musculus RNA-Seq
SRR7124018 PRJNA464051 Mus musculus RNA-Seq
SRR7124019 PRJNA464051 Mus musculus RNA-Seq
SRR7124020 PRJNA464051 Mus musculus RNA-Seq
SRR7124021 PRJNA464051 Mus musculus RNA-Seq
SRR7124022 PRJNA464051 Mus musculus RNA-Seq
SRR7124023 PRJNA464051 Mus musculus Ribo-Seq
SRR7124024 PRJNA464051 Mus musculus Ribo-Seq
SRR7124025 PRJNA464051 Mus musculus Ribo-Seq
SRR7124026 PRJNA464051 Mus musculus Ribo-Seq
SRR7124027 PRJNA464051 Mus musculus Ribo-Seq
SRR7124028 PRJNA464051 Mus musculus Ribo-Seq
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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