Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
Tarbier, Marcel ; Mackowiak, Sebastian D. ; Sekar, Vaishnovi ; Bonath, Franziska ; Yapar, Etka LU
; Fromm, Bastian
; Faridani, Omid R.
; Biryukova, Inna
and Friedländer, Marc R.
(2026)
In Genome Research
- Abstract
- microRNAs are small RNA molecules that can repress the expression of protein-coding genes post-transcriptionally. Previous studies have shown that microRNAs can also have alternative functions, including influencing target expression variation and covariation, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells (mESCs) by genetically deleting Drosha, leading to global loss of microRNAs. We apply complementary single-cell RNA-seq methods to study the variation of the targets and the microRNAs themselves, and transcriptional inhibition to measure target half-lives. We find that microRNAs form four distinct coexpression groups across single... (More)
- microRNAs are small RNA molecules that can repress the expression of protein-coding genes post-transcriptionally. Previous studies have shown that microRNAs can also have alternative functions, including influencing target expression variation and covariation, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells (mESCs) by genetically deleting Drosha, leading to global loss of microRNAs. We apply complementary single-cell RNA-seq methods to study the variation of the targets and the microRNAs themselves, and transcriptional inhibition to measure target half-lives. We find that microRNAs form four distinct coexpression groups across single cells. In particular, the mir-290 and the mir-182 genome clusters are abundantly, variably, and inversely expressed. Some cells have global biases toward specific miRNAs originating from either end of the hairpin precursor, suggesting the presence of unknown regulatory cofactors. We find that microRNAs generally increase variation and covariation of their targets at the RNA level, but we also find microRNAs such as miR-182 that appear to have opposite functions. In particular, microRNAs that are themselves variable in expression, such as miR-291a, are more likely to induce covariations. In summary, we apply genetic perturbation and multiomics to give the first global picture of microRNA dynamics at the single-cell level.
(Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/c2d5a87f-58ea-45ab-a182-afd6ad800698
- author
- Tarbier, Marcel
; Mackowiak, Sebastian D.
; Sekar, Vaishnovi
; Bonath, Franziska
; Yapar, Etka
LU
; Fromm, Bastian
; Faridani, Omid R.
; Biryukova, Inna
and Friedländer, Marc R.
- organization
- publishing date
- 2026-01-12
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Genome Research
- publisher
- Cold Spring Harbor Laboratory Press (CSHL)
- external identifiers
-
- pmid:41526192
- ISSN
- 1549-5469
- DOI
- 10.1101/gr.279914.124
- language
- English
- LU publication?
- yes
- id
- c2d5a87f-58ea-45ab-a182-afd6ad800698
- alternative location
- http://genome.cshlp.org/lookup/doi/10.1101/gr.279914.124
- date added to LUP
- 2026-01-14 10:26:37
- date last changed
- 2026-01-20 16:32:22
@article{c2d5a87f-58ea-45ab-a182-afd6ad800698,
abstract = {{microRNAs are small RNA molecules that can repress the expression of protein-coding genes post-transcriptionally. Previous studies have shown that microRNAs can also have alternative functions, including influencing target expression variation and covariation, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells (mESCs) by genetically deleting Drosha, leading to global loss of microRNAs. We apply complementary single-cell RNA-seq methods to study the variation of the targets and the microRNAs themselves, and transcriptional inhibition to measure target half-lives. We find that microRNAs form four distinct coexpression groups across single cells. In particular, the mir-290 and the mir-182 genome clusters are abundantly, variably, and inversely expressed. Some cells have global biases toward specific miRNAs originating from either end of the hairpin precursor, suggesting the presence of unknown regulatory cofactors. We find that microRNAs generally increase variation and covariation of their targets at the RNA level, but we also find microRNAs such as miR-182 that appear to have opposite functions. In particular, microRNAs that are themselves variable in expression, such as miR-291a, are more likely to induce covariations. In summary, we apply genetic perturbation and multiomics to give the first global picture of microRNA dynamics at the single-cell level.<br/>}},
author = {{Tarbier, Marcel and Mackowiak, Sebastian D. and Sekar, Vaishnovi and Bonath, Franziska and Yapar, Etka and Fromm, Bastian and Faridani, Omid R. and Biryukova, Inna and Friedländer, Marc R.}},
issn = {{1549-5469}},
language = {{eng}},
month = {{01}},
publisher = {{Cold Spring Harbor Laboratory Press (CSHL)}},
series = {{Genome Research}},
title = {{Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells}},
url = {{http://dx.doi.org/10.1101/gr.279914.124}},
doi = {{10.1101/gr.279914.124}},
year = {{2026}},
}