The body's ability to cope with a variety of stressors is critical to maintaining health, and the failure of this adaptive stress response can trigger or worsen many diseases
A new study led by researchers at Massachusetts General Hospital (MGH) and published in the journal Advanced Science shows that cells normally release certain RNA molecules called tDRs, In response to stressors, different tDRs may act as markers of cellular stress in different diseases
"RNA molecules have long been thought of as messengers between DNA (the genetic code) and proteins (the cell's functional molecules); however, over the past decade, researchers have discovered new functions for RNAs that cannot be converted into proteins -- so-called noncoding RNAs," said senior author Saumya Das, Ph.
, co-director of MGH's Resynchronization and Advanced Cardiac Therapy Program
Das notes that there are a growing number of noncoding RNAs with different functions, and among these, a new type of RNA is discovered from so-called transfer RNAs, whose function is usually to help synthesize proteins from traditional messenger RNAs
These RNAs, known as tRNA-derived small RNAs (tDRs), are produced when larger "parental" tRNAs are cleaved into smaller versions by stress-activating enzymes
By studying various human and rat cells under three stressors -- nutrient deprivation, hypoxia, and oxidative stress -- that are frequently present in many disease states, Das and colleagues A comprehensive analysis of intracellular and extracellular tDRs was performed in different stress responses
They also found that key proteins called RNases are important for extracellular TDR production and stability
"While TDRs play an important role in cellular function, we also found that TDRs are released by cells and that they may act as markers of cellular stress in different diseases," said Dr.
Guoping Li, first author of the study, MGH and a medical lecturer at Harvard Medical School
"We found that different types of stress signals can affect cellular and extracellular tDRs in different types of cells, and these stress signals have 'signatures'
The team created a stress signaling map of cellular and extracellular tDRs that can be used not only as an indicator of disease, but also as a starting point for scientists interested in studying the role of different tDRs in cancer, fibrosis, and other diseases
Das and his colleagues are focusing on one such tDR and its role in kidney disease
Journal Reference :
Guoping Li, Aidan C.
Manning, Alex Bagi, Xinyu Yang, Priyanka Gokulnath, Michail Spanos, Jonathan Howard, Patricia P.
Chan, Thadryan Sweeney, Robert Kitchen, Haobo Li, Brice D.
Laurent, Sary F.
Aranki, Maria I.
Kontaridis, Louise C.
Laurent, Kendall Van Keuren‐Jensen, Jochen Muehlschlegel, Todd M.
Lowe, Saumya Das.
Distinct Stress‐Dependent Signatures of Cellular and Extracellular tRNA‐Derived Small RNAs .
Advanced Science , 2022; 2200829 DOI: 10.