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LENG8 Functions as a Quality Control Checkpoint for Nuclear Retention and Degradation of Misprocessed RNAs

GSE299756 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2025/08/18 Platform GPL34284Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 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
Homo sapiens (human)
Samples
30 samples: 10 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
LENG8 mediates RNA nuclear retention and degradation in eukaryotesbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Quality control is essential for maintaining proper gene expression. For example, aberrantly processed RNAs are retained and degraded in the nucleus, and defects in this process have been linked to various diseases, including cancer and neurodegeneration. However, the underlying mechanisms of RNA nuclear retention and degradation remain poorly understood.
Read the full summary ↓
Through a genome wide CRISPR screen, we identified not only known factors involved in nuclear RNA degradation but also candidate proteins mediating RNA nuclear retention, including the poorly characterized protein LENG8. Our findings reveal that LENG8 is recruited to pre-mRNAs by splicing factors, including components of the U1 snRNP. Once RNA-bound, LENG8 is both necessary and sufficient to sequester RNA in the nucleus. Depletion of LENG8 leads to the leakage of intron containing RNAs and numerous nuclear noncoding RNAs into the cytoplasm, demonstrating its crucial role in RNA retention. Mechanistically, we further discovered that LENG8 lacks a specific region required for forming an intact TREX2 complex, unlike its paralog GANP. As a result, LENG8 retains misprocessed RNAs in the nucleus through a dominant-negative mechanism of TREX2/GANP, despite its ability to recruit TREX and the PCID2-SEM1 complex. Additionally, LENG8 interacts with the ZFC3H1-MTR4-exosome complex to degrade nuclear-retained RNAs, linking it to both RNA retention and degradation pathways. In conclusion, our study uncovers a novel mechanism of gene expression quality control, highlighting LENG8 as a key regulator of RNA nuclear retention and degradation, with potential implications for human disease.
Published in
LENG8 mediates RNA nuclear retention and degradation in eukaryotes
Tian L, Liu L, Yoon Y et al. · bioRxiv : the preprint server for biology 2025 · PMID 40832163 · doi:10.1101/2025.08.14.670437
This dataset
Open GSE299756 in finder → Find more human 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 GSE299756_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 PRJNA1276448 and SRA study SRP592086. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40832163) ↗
Study design
10 conditions, mostly in triplicate
control, cytoplasm mRNA-seq, ×3 control, nucleus mRNA-seq, ×3 LENG8-depletion, cytoplasm mRNA-seq, ×3 LENG8-depletion, nucleus mRNA-seq, ×3 control,cytoplasm, ×3 control,nucleus, ×3 control,total RNA, ×3 LENG8-depletion,cytoplasm, ×3 +3 more

Supports a between-group comparison across 29 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 29 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
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