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Plagl1 and Lrrc58 control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503 [AGO-CLASH]

GSE299946 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2025/11/11 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 10 conditions, mostly in duplicateGroups 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
Plagl1 and Lrrc58 control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503Genes & development · 2026
Summary (written by the submitters)
Precise control of microRNA (miRNA) expression is critical for normal development. An important mechanism of miRNA regulation is target-directed microRNA degradation (TDMD), a pathway in which the binding of miRNAs to specialized trigger RNAs induces ubiquitylation and decay of associated Argonaute (AGO) proteins by the ZSWIM8 ubiquitin ligase.
Read the full summary ↓
ZSWIM8-deficient mice exhibit reduced body size, cardiopulmonary and neurodevelopmental defects, and perinatal lethality. Despite widespread dysregulation of miRNAs in these animals, the vast majority of presumptive trigger RNAs that induce decay of ZSWIM8-regulated miRNAs remain undefined. Here, using AGO crosslinking and sequencing of hybrids (AGO-CLASH), a high-throughput method for identifying miRNA binding sites, we report the identification of Plagl1 as a trigger for TDMD of miR-322-5p, and Lrrc58 and Malat1 as TDMD triggers for miR-503-5p in mouse embryonic fibroblasts (MEFs). In mice, deletion of the miR-322-5p and miR-503-5p trigger sites in the Plagl1 and Lrrc58 3' UTRs, respectively, abrogated TDMD of these miRNAs and resulted in miR-322/503-dependent embryonic growth restriction, recapitulating a key feature of the Zswim8—/— phenotype. Thus, these results demonstrate that the transcripts encoding Plagl1 and Lrrc58 regulate mammalian body size by inducing degradation of miR-322-5p and miR-503-5p and provide a valuable resource for identification of additional TDMD triggers.
Published in
Plagl1 and Lrrc58 control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503
LaVigne CA, Han J, Zhang H et al. · Genes & development 2026 · PMID 41213800 · doi:10.1101/gad.353138.125
This dataset
Open GSE299946 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 GSE299946_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 PRJNA1277636 and SRA study SRP592557. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41213800) ↗
Study design
10 conditions, mostly in duplicate
AGO-CLASH_WT_Brain ×2 AGO-CLASH_WT_Lung ×2 AGO-CLASH_ZSWIM8 KO_Brain ×2 AGO-CLASH_ZSWIM8 KO_Lung ×2 AGO-CLASH_WT_Brain-1023-enriched ×2 AGO-CLASH_WT_Brain-1024-enriched ×2 AGO-CLASH_WT_Lung-1024-enriched ×2 AGO-CLASH_ZSWIM8 KO_Brain-1023-enriched ×2 +2 more

Supports a between-group comparison across 20 samples.

How we read this: 10 replicated groups read from 20 sample titles; they account for 20 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
Datasets on a similar topic

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