TitleDynamic expression of tRNA-derived small RNAs define cellular states.
Publication TypeJournal Article
Year of Publication2019
AuthorsKrishna S, Yim DGr, Lakshmanan V, Tirumalai V, Koh JLy, Park JEun, Cheong JKong, Low JLeng, Lim MJs, Sze SKwan, Shivaprasad P, Gulyani A, Raghavan S, Palakodeti D, DasGupta R
JournalEMBO Rep
Date Published2019 Jul

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell-state transitions remain unclear. Expression analysis of tsRNAs in distinct heterologous cell and tissue models of stem vs. differentiated states revealed a differentiation-dependent enrichment of 5'-tsRNAs. We report the identification of a set of 5'-tsRNAs that is upregulated in differentiating mouse embryonic stem cells (mESCs). Notably, interactome studies with differentially enriched 5'-tsRNAs revealed a switch in their association with "effector" RNPs and "target" mRNAs in different cell states. We demonstrate that specific 5'-tsRNAs can preferentially interact with the RNA-binding protein, Igf2bp1, in the RA-induced differentiated state. This association influences the transcript stability and thereby translation of the pluripotency-promoting factor, c-Myc, thus providing a mechanistic basis for how 5'-tsRNAs can modulate stem cell states in mESCs. Together our study highlights the role of 5'-tsRNAs in defining distinct cell states.

Alternate JournalEMBO Rep.
PubMed ID31267708
PubMed Central IDPMC6607006
Grant List500160/Z/09/Z / / DBT India Alliance (India Alliance) /
DST/SJF/LSA-02/2015-16 / / Department of Science and Technology, Ministry of Science and Technology (DST) /
/ / Agency for Science, Technology and Research (A*STAR) /
/ / Wellcome Trust / United Kingdom
BT/PR8655/AGR/36/759/2013 / / Department of Biotechnology, Ministry of Science and Technology (DBT) /