Journal
GENES
Volume 13, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/genes13111925
Keywords
miRNA processing; C19MC; miRNA cluster; human pluripotent stem cells; differentiation
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Funding
- National Brain Research Program (NAP) of Hungary [2017-1.2.1-NKP-2017-00002]
- National Research, Development and Innovation Office [OTKA-K128369, 2018-1.2.1-NKP-2018-00005]
- Hungarian Academy of Sciences [PC-II-12/2022]
- Centre of Excellence of the Hungarian Academy of Sciences
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Studies have shown that DGCR8 heterozygous mutation has a modest effect on mRNA level but a significant decrease at the protein level, while not affecting self-renewal and trilineage differentiation capacity of hESCs.
Maturation of microRNAs (miRNAs) begins by the Microprocessor complex, containing the Drosha endonuclease and its partner protein, DiGeorge Syndrome Critical Region 8 (DGCR8). Although the main function of the two proteins is to coordinate the first step of precursor miRNAs formation, several studies revealed their miRNA-independent functions in other RNA-related pathways (e.g., in snoRNA decay) or, for the DGCR8, the role in tissue development. To investigate the specific roles of DGCR8 in various cellular pathways, we previously established a human embryonic stem-cell (hESC) line carrying a monoallelic DGCR8 mutation by using the CRISPR-Cas9 system. In this study, we genetically characterized single-cell originated progenies of the cell line and showed that DGCR8 heterozygous mutation results in only a modest effect on the mRNA level but a significant decrease at the protein level. Self-renewal and trilineage differentiation capacity of these hESCs were not affected by the mutation. However, partial disturbance of the Microprocessor function could be revealed in pri-miRNA processing along the human chromosome 19 miRNA cluster in several clones. With all these studies, we can demonstrate that the mutant hESC line is a good model to study not only miRNA-related but also other noncanonical functions of the DGCR8 protein.
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