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Non-canonical proteolytic activation of RNase L by SARS-CoV-2 3CLpro offsets inactivation of OAS1 antiviral signaling

GSE324550 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2026/04/01 Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 14 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
14 samples: 7 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.
Summary (written by the submitters)
Upon sensing viral dsRNA, interferon-stimulated oligoadenylate synthetases (OAS) synthesize 2´-5´oligoadenylates that activate ribonuclease L (RNase L) to restrict viral replication. The predominant protective OAS during SARS-CoV-2 infection is the membrane-anchored OAS1 isoform p46. We show that SARS-CoV-2 3C-like main protease (3CL pro /M pro ) cleaves p46 at 381 STLQ 384 ↓A, removing the prenylated Cys 397 anchor, releasing p46 into the cytosol, and decreasing antiviral restriction.
Read the full summary ↓
Unexpectedly, RNase L continues to restrict SARS-CoV-2 replication in p46-null cells. We identify RNase L as a second substrate within the OAS–RNase L pathway. Cleavage at 406 SCLQ 409 ↓S removes an inhibitory N-terminal domain, generating RNase L (410–741), a proteolytically activated product that restricts viral replication. A non-cleavable RNase L (Gln409Ala) mutant lacks antiviral activity in p46-null cells, confirming this non-canonical activation mechanism. RNA-seq revealed that the proteolytically activated RNase exhibits altered specificity toward cellular mRNA targets and that 3CL pro indirectly suppresses OAS3 transcripts without directly cleaving OAS3. We propose that the conserved 3CL pro -sensitive motif in RNase L functions as a failsafe tripwire that constrains complete loss of antiviral restriction despite simultaneous evasion of OAS1 p46. Thus, SARS-CoV-2 replication dynamics are intrinsically balanced by viral proteolysis within the OAS–RNase L axis, sufficient for polyprotein processing but countered by protease-triggered activation of RNase L and downstream antiviral restriction.
This dataset
Open GSE324550 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 GSE324550_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 PRJNA1435780 and SRA study SRP682855. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 conditions, mostly in duplicate
RNaseL biol ×2 RNase L (410–741) biol ×2 RNase L (1–409) biol ×2 3CL pro (24 h) biol ×2 3CL pro (Cys145Ala) (24 h) biol ×2 3CL pro (48 h) biol ×2 3CL pro (Cys145Ala) (48 h) biol ×2

Supports a between-group comparison across 14 samples.

How we read this: 7 replicated groups read from 14 sample titles; they account for 14 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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