GEO series

Characterization of ribosome stalling and no-go mRNA decay stimulated by the Fragile X protein, FMRP

GSE254586 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2024/08/28 Platform GPL21493

At a glance

RNA-seq (gene expression) · mouse · 18 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 18 samples: 6 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Characterization of ribosome stalling and no-go mRNA decay stimulated by the fragile X protein, FMRPThe Journal of biological chemistry · 2024

Summary (written by the submitters)

Loss of functional fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS) and is the leading monogenic cause of autism spectrum disorders and intellectual disability. FMRP is most notably a translational repressor and is thought to inhibit translation elongation by stalling ribosomes as FMRP-bound polyribosomes from brain tissue are resistant to puromycin and nuclease treatment.

Read the full summary ↓

Here, we present data showing that the C-terminal non-canonical RNA-binding domain of FMRP is essential and sufficient to induce puromycin-resistant mRNA•ribosome complexes. Given that stalled ribosomes can stimulate ribosome collisions and no-go mRNA decay (NGD), we tested the ability of FMRP to drive NGD of its target transcripts in neuroblastoma cells. Indeed, FMRP and ribosomal proteins, but not PABPC1, were enriched in isolated nuclease-resistant disomes compared to controls. Using siRNA knockdown and RNA-seq, we identified 16 putative FMRP-mediated NGD substrates, many of which encode proteins involved in neuronal development and function. Increased mRNA stability of the putative substrates was also observed when either FMRP was depleted or NGD was prevented via RNAi. Taken together, these data support that FMRP stalls ribosomes and can stimulate NGD in cells, albeit on a small number of transcripts, revealing an unappreciated role of FMRP that would be misregulated in FXS when FMRP is lost.

Published in

Characterization of ribosome stalling and no-go mRNA decay stimulated by the fragile X protein, FMRP

Scarpitti MR, Pastore B, Tang W et al. · The Journal of biological chemistry 2024 · PMID 38971316 · doi:10.1016/j.jbc.2024.107540

This dataset

Open GSE254586 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE254586_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1071088 and SRA study SRP486843. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38971316) ↗

Study design

6 conditions, mostly in triplicate

fmrp_siRNA_A ×3 fmrp_siRNA_B ×3 neg_control_siRNA_A ×3 neg_control_siRNA_B ×3 znf_siRNA_A ×3 znf_siRNA_B ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8046659 fmrp_siRNA_A1 fmrp_siRNA_A
GSM8046660 fmrp_siRNA_A2 fmrp_siRNA_A
GSM8046661 fmrp_siRNA_A3 fmrp_siRNA_A
GSM8046662 fmrp_siRNA_B1 fmrp_siRNA_B
GSM8046663 fmrp_siRNA_B2 fmrp_siRNA_B
GSM8046664 fmrp_siRNA_B3 fmrp_siRNA_B
GSM8046665 neg_control_siRNA_A1 neg_control_siRNA_A
GSM8046666 neg_control_siRNA_A2 neg_control_siRNA_A
GSM8046667 neg_control_siRNA_A3 neg_control_siRNA_A
GSM8046668 neg_control_siRNA_B1 neg_control_siRNA_B
GSM8046669 neg_control_siRNA_B2 neg_control_siRNA_B
GSM8046670 neg_control_siRNA_B3 neg_control_siRNA_B
GSM8046671 znf_siRNA_A1 znf_siRNA_A
GSM8046672 znf_siRNA_A2 znf_siRNA_A
GSM8046673 znf_siRNA_A3 znf_siRNA_A
GSM8046674 znf_siRNA_B1 znf_siRNA_B
GSM8046675 znf_siRNA_B2 znf_siRNA_B
GSM8046676 znf_siRNA_B3 znf_siRNA_B

Datasets on a similar topic

GSE291701 FMRP Regulates Neuronal RNA Granules Containing Stalled Ribosomes, Not Where Ribosomes Stall 36 samples shares fmrp, ribosome
GSE26809 FMRP Associates with Polyribosomes 26 samples shares fmrp, ribosome
GSE159295 Translation-dependent and independent mRNA decay occur through mutually exclusive pathways that are defined by ribosome density during T Cell activation [RNA-Seq] 105 samples shares ribosome, decay
GSE291652 Codon-specific ribosome stalling reshapes translational dynamics during branched-chain amino acid starvation 18 samples shares ribosome, stalling
GSE242038 The nucleolar aberrancies that drive ribosome impairment induced by RNA binding proteins are hallmarks of aging 9 samples shares ribosome, protein
GSE286381 Neuronal activation triggers rapid biphasic FMRP-mediated translational control linking synaptic and nuclear regulation [RiboTag] 32 samples shares fmrp
GSE327880 Neuronal activation triggers rapid biphasic FMRP-mediated translational control linking synaptic and nuclear regulation 51 samples shares fmrp
GSE45148 HITS-CLIP analysis of FMRP mRNA binding sites from P11-P25 mouse brain polysomes 9 samples shares fmrp

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