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| Status |
Public on Jun 27, 2022 |
| Title |
Cellular and extracellular tRNA-derived fragments demonstrate distinct signatures in cellular stress |
| Organisms |
Homo sapiens; Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression . tRNA and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. However, systematic characterization of tDRs have been challenged by the technical difficulties in accurately profiling tDRs with normal small RNA sequencing techniques due to the presence of RNA modifications. Here we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDRs expression in a variety of human and rat cells during common stress responses, including nutrition deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs, and comprise signatures that improve discrimination of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in 4 different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNA from patients on cardiopulmonary bypass with significant overlap with the signatures of nutrition depravation and oxidative stress in our cellular models, providing preliminary in vivo correlation of our findings. Future application of our findings to human disease models may have promise in yielding novel biomarkers.
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| Overall design |
Cellular and extracellular tDRs expression profiles of 4 cell types under 4 different treatments (3 independent replicates for each condition)
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| Contributor(s) |
Li G, Manning A, Bagi A, Yang X, Howard J, Chan P, Sweeney T, Laurent B, Li H, Kontaridis M, Laurent LC, Van Keuren-Jensen K, Muehlschlegel JD, Kitchen R, Lowe TM, Das S |
| Citation(s) |
35373532 |
| Submission date |
May 04, 2021 |
| Last update date |
Jun 27, 2022 |
| Contact name |
Guoping Li |
| E-mail(s) |
gli21@mgh.harvard.edu
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| Organization name |
Massachusetts General Hospital
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| Department |
CVRC
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| Lab |
Dr. Saumya Das
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| Street address |
Cardiovascular Research Center, 185 Cambridge St, Simches 3.5000
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (96)
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| Relations |
| BioProject |
PRJNA727096 |
| SRA |
SRP318389 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE173806_Human_normalized_readcounts.csv.gz |
433.4 Kb |
(ftp)(http) |
CSV |
| GSE173806_Rat_normalized_readcounts.csv.gz |
426.1 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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