Dataset Information

3’tRNAAsp(GTC)-derived fragment links inflammation to post-transcriptional reprogramming in chondrocytes during osteoarthritis. [Primary Chondrocytes small RNA-seq]

ABSTRACT: Background/Aim: Transfer RNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs that dynamically respond to metabolic stressors and drive different pathological processes, yet their role in osteoarthritis (OA) remains poorly explored. We aimed to define the tRF landscape in OA and investigate the function of 3′tRFAsp(GTC) in chondrocyte stress adaptation and translational control. Methods: Ex vivo, cartilage specimens from OA patients and healthy donors were analyzed by small RNA sequencing to define disease-associated tRF signatures. In vitro, primary chondrocytes derived from OA patients were treated with lipopolysaccharide (LPS) to mimic the pro-inflammatory environment of OA. Functional studies included antisense oligonucleotide (ASO)-mediated 3′tRFAsp(GTC) inhibition, AGO2-RNA immunopreicipitation (RIP), polysome profiling, stress granule (SG) immunofluorescence, and differential protein analysis. Computational target prediction and pathway enrichment were used to explore tRF-mediated regulatory networks. Results: Both ex vivo OA cartilage and LPS-treated OA chondrocytes displayed upregulation of 3′tRFAsp(GTC) and 5′tRFGlu(CTC), indicating a shared inflammatory tRF signature. Silencing 3′tRFAsp(GTC) attenuated LPS-induced COX2 and MMP13 expression, prevented ER stress, and blocked SG assembly. RIP confirmed selective recruitment of 3′tRFAsp(GTC) into AGO2 complexes. Polysome profiling revealed association with 40S ribosomal subunits, mediating translational arrest and influencing selective mRNA expression. Predicted targets of upregulated tRFs were enriched in stress-adaptive, proteostasis, and translational control pathways, whereas downregulated tRFs modulated mitochondrial processes. Conclusions: 3′tRFAsp(GTC) emerges as crucial regulator linking inflammatory stress to translational control and SG dynamics in OA. tRFs thus could represent a novel therapeutic targets to counteract chronic inflammatory stress in degenerative joint disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE316834 | GEO | 2026/01/27

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE316834_Primary_Chondrocytes_tRF_LPS_vs_Ctrl_DESeq2_Normalized_counts.csv.gz	Csv
	GSE316834_Primary_Chondrocytes_tRF_LPS_vs_Ctrl_raw_counts.csv.gz	Csv
	GSE316834_Primary_Chondrocytes_tRF_annotation_MINTmap_MINTbase_LPS_vs_CTRL.csv.gz	Csv

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Project description:Background/Aim: Transfer RNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs that dynamically respond to metabolic stressors and drive different pathological processes, yet their role in osteoarthritis (OA) remains poorly explored. We aimed to define the tRF landscape in OA and investigate the function of 3′tRFAsp(GTC) in chondrocyte stress adaptation and translational control. Methods: Ex vivo, cartilage specimens from OA patients and healthy donors were analyzed by small RNA sequencing to define disease-associated tRF signatures. In vitro, primary chondrocytes derived from OA patients were treated with lipopolysaccharide (LPS) to mimic the pro-inflammatory environment of OA. Functional studies included antisense oligonucleotide (ASO)-mediated 3′tRFAsp(GTC) inhibition, AGO2-RNA immunopreicipitation (RIP), polysome profiling, stress granule (SG) immunofluorescence, and differential protein analysis. Computational target prediction and pathway enrichment were used to explore tRF-mediated regulatory networks. Results: Both ex vivo OA cartilage and LPS-treated OA chondrocytes displayed upregulation of 3′tRFAsp(GTC) and 5′tRFGlu(CTC), indicating a shared inflammatory tRF signature. Silencing 3′tRFAsp(GTC) attenuated LPS-induced COX2 and MMP13 expression, prevented ER stress, and blocked SG assembly. RIP confirmed selective recruitment of 3′tRFAsp(GTC) into AGO2 complexes. Polysome profiling revealed association with 40S ribosomal subunits, mediating translational arrest and influencing selective mRNA expression. Predicted targets of upregulated tRFs were enriched in stress-adaptive, proteostasis, and translational control pathways, whereas downregulated tRFs modulated mitochondrial processes. Conclusions: 3′tRFAsp(GTC) emerges as crucial regulator linking inflammatory stress to translational control and SG dynamics in OA. tRFs thus could represent a novel therapeutic targets to counteract chronic inflammatory stress in degenerative joint disease.

Project description:Background: Colorectal liver metastases (CRLM) are the leading cause of colorectal cancer (CRC)-related mortality. Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNAs (sncRNA), regulate gene expression, stress response, and immune functions in cancer. While tRFs are increasingly implicated in CRC progression, their prognostic significance in CRLM remains unknown. This study investigates the abundance and prognostic value of genomic (ge) and mitochondrial (mt) tRFs in CRLM. Methods: This single-center retrospective cohort study included all CRLM patients who underwent curative liver resection between January 2012 and December 2015. Small RNA sequencing (sRNA-seq) quantified ge- and mt-tRF expression in tumor samples. Event-free survival (EFS) was the primary outcome, and the impact of tRFs on EFS was assessed using Cox regression, spline modeling of the effects of tRFs on EFS, and network analysis. Results: Among 588 screened samples, 40 met eligibility criteria (18 females [45%], median age 64 [42-79]). A total of 432 tRFs were identified, with ge-tRFs (67%) being more abundant than mt-tRFs (33%). Using spline regressions, tRFs were classified into 10 ten prognostic groups. High ge-tRF abundance correlated predominantly with unfavorable EFS (FDR<0.2; 94%), whereas mt-tRFs were significantly (p<0.001; χ2 test) more often associated with favorable EFS (FDR<0.2; 26%). Network analysis of tRF abundance correlations revealed a significantly higher intra-mitochondrial network density compared to the intra-genomic tRF network. However, no significant differences in network structure were observed between prognostically significant vs. non-significant or favorable vs. unfavorable tRFs. Finally, key tRF candidates, such as tRHalve3-His-CAU (mt-tRF) or tRNAleader-Gln-UUG (mt-tRF) paired with tRFmisc-Tyr-GTA (ge-tRF), remained independent prognostic markers after adjustment for clinical covariates. Conclusion: This study provides the first comprehensive characterization of tRF expression in CRLM, revealing distinct prognostic roles for ge- and mt-tRFs. While ge-tRFs were predominantly associated with unfavorable prognosis, a subset of mt-tRFs demonstrated a favorable impact on EFS. These findings highlight the potential of tRFs as novel prognostic biomarkers and therapeutic targets in CRLM, warranting validation in prospective studies.

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3’tRNAAsp(GTC)-derived fragment links inflammation to post-transcriptional reprogramming in chondrocytes during osteoarthritis. [Primary Chondrocytes small RNA-seq]

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