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Distinct Stress-Dependent Signatures of Cellular and Extracellular tRNA-Derived Small RNAs
Guoping Li1, Aidan C Manning2, Alex Bagi2
1Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 4, 2022
Summary
Stress responses involve transfer RNA-derived small RNAs (tDRs). Researchers developed a new sequencing method to reveal distinct extracellular tDR signatures, which show promise as disease biomarkers, even in patient plasma.
Area of Science:
- Molecular Biology
- Biochemistry
- Genomics
Background:
- Cellular stress responses are critical in disease development.
- Transfer RNA-derived small RNAs (tDRs) are implicated in stress responses.
- RNA modifications on tDRs hinder accurate quantification via standard sequencing.
Purpose of the Study:
- To comprehensively profile cellular and extracellular tDRs during stress responses.
- To investigate the potential of tDRs as biomarkers for stress-induced diseases.
- To elucidate the biogenesis and regulation of stress-responsive tDRs.
Main Methods:
- Employed AlkB-facilitated methylation sequencing for tDR profiling.
- Analyzed tDR abundances in various cell types under different stress conditions.
- Compared extracellular tDR fragmentation signatures with microRNAs (miRNAs) and observed patterns in patient plasma.
Main Results:
- Generated a detailed landscape of cellular and extracellular tDR abundances.
- Extracellular tDRs exhibit unique fragmentation signatures distinct from intracellular tDRs and miRNAs, serving as effective stress indicators.
- These tDR signatures were identified in plasma from patients undergoing cardiopulmonary bypass, and angiogenin/RNASE1 were found to modulate tDR levels.
Conclusions:
- Extracellular tDR fragmentation signatures are robust indicators of cellular stress.
- tDRs, particularly extracellular ones, represent promising novel biomarkers for stress-related conditions.
- Angiogenin, RNASE1, and AGO2 play roles in the biogenesis and regulation of stress-responsive tDRs.
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