MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development
Open accessAbstract
Alternative splicing transitions have been identified recently as a conserved component of vertebrate heart remodeling during postnatal development. Here we report that the targeted deletion of Dicer , specifically in adult mouse myocardium, reveals the role of microRNAs (miRNAs) in regulating networks of postnatal splicing transitions and in maintaining adult splicing programs. We demonstrate a direct role for miR-23a/b in the dramatic postnatal down-regulation of CUGBP and ETR-3-like factor (CELF) proteins that regulate nearly half of developmentally regulated splicing transitions in the heart. These findings define a hierarchy in which rapid postnatal up-regulation of specific miRNAs controls expression of alternative splicing regulators and the subsequent splicing transitions of their downstream targets.
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The interplay between miRNAs and RBPs leads to global changes in gene expression in which miRNAs control expression of RBPs to regulate tissue-specific RNA processing decisions.
“The interplay between miRNAs and RBPs leads to global changes in gene expression in which miRNA(s) control expression of RBPs to regulate tissue-specific RNA processing decisions (Boutz et al. 2007; Makeyev et al. 2007; Kalsotra et al. 2010; van Kouwenhove et al. 2011; Misra et al. 2020)”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Kalsotra et al. 2010
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The impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592 · see citing works
Widespread changes in protein synthesis induced by microRNAs
Selbach, M., Schwanhäusser, B., Thierfelder, N., Fang, Z., Khanin, R., & Rajewsky, N. (2008) · Nature · doi:10.1038/nature07228 · Cited by 3,429 · cited 1× · see citing works
“While miRNA-mediated regulation stimulates quantitative changes in protein and mRNA expression (Baek et al. 2008; Selbach et al. 2008), alternative pre-mRNA splicing controls qualitative gene output in the expression of diverse mRNA isoforms (Blencowe 2006).”
BackgroundMorphogenesis in skin is governed by discrete sets of differentially expressed microRNAs
Yi, R., O'Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., & Fuchs, E. (2006) · Nature Genetics · doi:10.1038/ng1744 · Cited by 555 · see citing works
MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development
Boutz, P. L., Chawla, G., Stoilov, P., & Black, D. L. (2007) · Genes & Development · doi:10.1101/gad.1500707 · Cited by 304 · see citing works
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Function of alternative splicing
Kelemen, O., Convertini, P., Zhang, Z., Wen, Y., Shen, M., Falaleeva, M., & Stamm, S. (2013) · Gene · doi:10.1016/j.gene.2012.07.083 · Cited by 743 · see citing works
Alternative splicing rewires Hippo signaling pathway in hepatocytes to promote liver regeneration
Bangru, S., Arif, W., Seimetz, J., Bhate, A., Chen, J., Rashan, E. H., Carstens, R. P., Anakk, S., & Kalsotra, A. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0129-2 · Cited by 85 · see citing works
Self-citationCalarco, J. A., Zhen, M., & Blencowe, B. J. (2011) · RNA · doi:10.1261/rna.2603911 · Cited by 72 · see citing works
Yang, J., Nie, Y., Wang, F., Hou, J., Cong, X., Hu, S., & Chen, X. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.05.005 · Cited by 30 · see citing works
ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation
Bangru, S., Chen, J., Baker, N., Das, D., Chembazhi, U. V., Derham, J. M., Chorghade, S., Arif, W., Alencastro, F., Duncan, A. W., et al. (2025) · Genes & Development · doi:10.1101/gad.352129.124 · Cited by 4 · see citing works
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- Authors
- Kalsotra, A., Wang, K., Li, P.-F., & Cooper, T. A.
- Affiliations
- Baylor College of Medicine (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Cooper, Thomas A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-03-18
- Volume
- 24
- Issue
- 7
- Pages
- 653-658
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2849122
- OpenAlex
- W2162606181
- Cited by
- 129
- References
- 4
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 8 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 12 · 2013: 11 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL045565)
- National Institute of General Medical Sciences (R01GM076493)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045653)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- microRNA, alternative splicing, postnatal heart development, Dicer, cardiac remodeling, splicing regulators, myocardium
- MeSH terms
- CELF1 Protein, Animals, Cell Line, Endoribonucleases, Heart, Down-Regulation, Up-Regulation, RNA-Binding Proteins, Alternative Splicing, MicroRNAs, Ribonuclease III, Mice, DEAD-box RNA Helicases, Gene Knockdown Techniques
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