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Functional characterization of tRNA-derived small RNAs in stem cells

Muthukumar, Sowndarya LU orcid ; Tucciarone, Silvia LU ; Germanos, Alexandre André LU and Bellodi, Cristian LU (2025) In Methods in Enzymology 711. p.261-282
Abstract

Transfer RNA (tRNA)-derived RNAs (tDRs) are abundant small RNAs with emerging roles in development and tumorigenesis. Increasing evidence indicates that tDRs regulate stem cell homeostasis and differentiation, often altered in disease, highlighting the importance of fully characterizing their role in stem cell biology. Multiple studies point to protein synthesis as a crucial target of tDR-mediated control of different stem cell types. Translation is a highly regulated process that integrates various input signals from cell-intrinsic and -extrinsic cues. Notably, tDRs largely impact translation initiation and ribosome biogenesis, driving critical adaptations of the stem cell proteome and balancing dynamic transitions between... (More)

Transfer RNA (tRNA)-derived RNAs (tDRs) are abundant small RNAs with emerging roles in development and tumorigenesis. Increasing evidence indicates that tDRs regulate stem cell homeostasis and differentiation, often altered in disease, highlighting the importance of fully characterizing their role in stem cell biology. Multiple studies point to protein synthesis as a crucial target of tDR-mediated control of different stem cell types. Translation is a highly regulated process that integrates various input signals from cell-intrinsic and -extrinsic cues. Notably, tDRs largely impact translation initiation and ribosome biogenesis, driving critical adaptations of the stem cell proteome and balancing dynamic transitions between self-renewal, proliferation, and cell-fate trajectories. Hematopoietic stem cells (HSCs) give rise to all circulating blood cells and exhibit exquisite sensitivity to tDR-mediated translation control impacting HSC homeostasis and differentiation. Significantly, defects in tDR levels and processing may drive malignant phenotypes in HSCs by supporting aberrant proteomic programs associated with leukemia transformation. While sequencing technologies have dramatically improved tDR detection and quantification, the specific mechanisms by which tDRs impact cellular phenotypes remain incompletely understood. With this increased resolution, further studies will lead to novel insights on the roles of tDRs in crucial stem cell phenotypes. In this chapter, we showcase useful protocols to characterize the molecular functions of tDRs in stem cell populations. We include methods to quantify the effects of tDR on protein synthesis and stem cell proliferation and differentiation. Finally, we highlight in vivo techniques to measure tDR impact on HSC engraftment potential in xenograft models.

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Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Development, HSCs, Stem cells, TDRs, Translation
host publication
Methods in Enzymology
series title
Methods in Enzymology
volume
711
pages
261 - 282
publisher
Academic Press
external identifiers
  • pmid:39952709
  • scopus:85211037405
ISSN
1557-7988
0076-6879
DOI
10.1016/bs.mie.2024.11.015
language
English
LU publication?
yes
id
38e9ee84-fe4b-44fd-9a77-75b0b7dce06d
date added to LUP
2025-01-31 15:31:45
date last changed
2025-07-05 04:19:06
@inbook{38e9ee84-fe4b-44fd-9a77-75b0b7dce06d,
  abstract     = {{<p>Transfer RNA (tRNA)-derived RNAs (tDRs) are abundant small RNAs with emerging roles in development and tumorigenesis. Increasing evidence indicates that tDRs regulate stem cell homeostasis and differentiation, often altered in disease, highlighting the importance of fully characterizing their role in stem cell biology. Multiple studies point to protein synthesis as a crucial target of tDR-mediated control of different stem cell types. Translation is a highly regulated process that integrates various input signals from cell-intrinsic and -extrinsic cues. Notably, tDRs largely impact translation initiation and ribosome biogenesis, driving critical adaptations of the stem cell proteome and balancing dynamic transitions between self-renewal, proliferation, and cell-fate trajectories. Hematopoietic stem cells (HSCs) give rise to all circulating blood cells and exhibit exquisite sensitivity to tDR-mediated translation control impacting HSC homeostasis and differentiation. Significantly, defects in tDR levels and processing may drive malignant phenotypes in HSCs by supporting aberrant proteomic programs associated with leukemia transformation. While sequencing technologies have dramatically improved tDR detection and quantification, the specific mechanisms by which tDRs impact cellular phenotypes remain incompletely understood. With this increased resolution, further studies will lead to novel insights on the roles of tDRs in crucial stem cell phenotypes. In this chapter, we showcase useful protocols to characterize the molecular functions of tDRs in stem cell populations. We include methods to quantify the effects of tDR on protein synthesis and stem cell proliferation and differentiation. Finally, we highlight in vivo techniques to measure tDR impact on HSC engraftment potential in xenograft models.</p>}},
  author       = {{Muthukumar, Sowndarya and Tucciarone, Silvia and Germanos, Alexandre André and Bellodi, Cristian}},
  booktitle    = {{Methods in Enzymology}},
  issn         = {{1557-7988}},
  keywords     = {{Development; HSCs; Stem cells; TDRs; Translation}},
  language     = {{eng}},
  pages        = {{261--282}},
  publisher    = {{Academic Press}},
  series       = {{Methods in Enzymology}},
  title        = {{Functional characterization of tRNA-derived small RNAs in stem cells}},
  url          = {{http://dx.doi.org/10.1016/bs.mie.2024.11.015}},
  doi          = {{10.1016/bs.mie.2024.11.015}},
  volume       = {{711}},
  year         = {{2025}},
}