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Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis

GSE284268 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2025/12/12 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 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
Homo sapiens (human)
Samples
20 samples: 5 conditions, mostly with about 4 replicates eachGroups 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
Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosisAtherosclerosis · 2026
Summary (written by the submitters)
Epitranscriptomic modifications on RNA play critical roles in stability, processing, and function, partly by influencing interactions with RNA-binding proteins and receptors. The diverse role(s) of post-transcriptional RNA modifications on cell-free small non-coding RNAs (sRNA) remain poorly understood, particularly in disease contexts.
Read the full summary ↓
Although HDL confer many beneficial properties to health, HDL particles lose these features during atherosclerotic cardiovascular disease (ASCVD). As HDL transport sRNA fragments from classes of RNA known to harbor extensive modifications, we predicted that changes to regulatory modifications on HDL-sRNAs may contribute to HDL functionality changes in ASCVD. To assess HDL-RNA modification levels in ASCVD, total RNA were isolated from HDL of healthy subjects (CAC=0) and those with advanced atherosclerosis, as determined by coronary artery calcium (CAC) scores >21 Agatston units. HDL-RNA were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and AlkB-facilitated RNA (de)Methylation Sequencing (ARM-seq). LC-MS/MS revealed elevated levels of modified nucleosides in HDL-sRNAs from ASCVD subjects, while ARM-seq detected an enrichment of m1A-modified sRNAs-derived from parent tRNAs (tDR), particularly tDR-ArgACG-1. To assess the impact of disease HDL on immune cells, primary macrophages were treated with HDL isolated from ASCVD (CAC+) and control subjects, and results showed that ASCVD-HDL directly induced expression of genes associated with immune signaling and cell adhesion, including TMEM123, a transmembrane protein linked to immune cell migration, adhesion, and cytoskeletal organization. In addition, recombinant HDL particles loaded with m1A-tDR-ArgACG-1 were found to significantly increase TMEM123 expression in treated primary macrophages. Together, these findings propose a model in which HDL-delivered m1A-HDL-tDRs directly stimulate immune signaling, macrophage activation, and pro-inflammatory sub-phenotypes within the atherosclerotic lesion. This study highlights HDL-associated RNA modifications as previously unrecognized contributors to immune modulation, with direct implications for targeting modified HDL-tDRs as a new approach to therapy for ASCVD.
Published in
Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis
Semler EM, Michell DL, Kingsley PJ et al. · Atherosclerosis 2026 · PMID 41380623 · doi:10.1016/j.atherosclerosis.2025.120584
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 GSE284268_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 PRJNA1198308 and SRA study SRP551433. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly with about 4 replicates each
hMDM, sHDL, WT tDR-1 ×4 hMDM, sHDL, m1A tDR-1 ×4 hMDM, sHDL, WT tDR-2 ×4 hMDM, sHDL, m1A tDR-2 ×4 hMDM, sHDL ×4

Supports a between-group comparison across 20 samples.

How we read this: 5 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
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