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Dynamic expression of tRNA‐derived small RNAs define cellular states
Author(s) -
Krishna Srikar,
Yim Daniel GR,
Lakshmanan Vairavan,
Tirumalai Varsha,
Koh Judice LY,
Park Jung Eun,
Cheong Jit Kong,
Low Joo Leng,
Lim Michelle JS,
Sze Siu Kwan,
Shivaprasad Padubidri,
Gulyani Akash,
Raghavan Srikala,
Palakodeti Dasaradhi,
DasGupta Ramanuj
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201947789
Subject(s) - biology , interactome , transfer rna , rna , microbiology and biotechnology , embryonic stem cell , heterologous , genetics , tandem affinity purification , computational biology , cellular differentiation , gene , biochemistry , affinity chromatography , enzyme
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.