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N6-Methyladenosine reader YTHDF3 regulate Sindbis virus release by incomplete selective autophagy flux maintenance through SQSTM1

GSE280392 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/10/01 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples
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)
N6-methyladenosine (m6A) is vital for RNA metabolism and function and is one of the most abundant internal RNA modifications. Recently, m6A has been indicated in regulating replication of multiple viruses; however, the role of m6A in typical arbovirus-alphavirus, is mainly elusive. Alphavirus containing several emerging and re-emerging pathogens that poses great threat to human health.
Read the full summary ↓
Here, we show that the prototype alphavirus, Sindbis virus (SINV), its replication is regulated by m6A readers. Of which, depleting YTHDF3 results in reduced SINV release but increased viral capsid within the cell. Mechanically, YTHDF3 bind and regulate the mRNA stability of SQSTM1, the major selective autophagy receptor, which targeting of capsid into autophagosomes. Furthermore, we found interaction between YTHDF3, SQSTM1 and capsid in pairs. K27 ubiquitination is the dominant modification for SINV capsid. Besides ubiquitin-associated (UBA) domain, the N-terminal domain of SQSTM1 has stronger interaction with capsid, highlighted the role of RL peptide mimic within the capsid. Further experiments revealed that the interaction between YTHDF3 and SQSTM1 protein relies on their YTH-domain and ZZ-type Zinc finger domain respectively. Together, these results highlight the role of m6A modification reader YTHDF3 in regulating selective autophagy during virus infection and provide new insights into alphavirus replication cycle.
This dataset
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.

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 GSE280392_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1178295 and SRA study SRP541437. Searching any of these in the dataset finder brings you back here.

Samples in this study

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