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Joint studies of TTK research groups make Genes cover


Researchers from two laboratories operating at the ELKH Research Centre for Natural Sciences (TTK), Institute of Enzymology, led by Ágota Apáti and Tamás Orbán respectively, investigated the expression of microRNAs playing an important role in the regulation of gene expression on a genetically modified stem cell line. A study presenting the results was published in the November 2022 issue of the prestigious scientific journal Genes, and at the request of the editors, the corresponding illustration on the joint collaborative publication was also selected for the cover page of that issue.


Maturation of microRNAs begins by the “Microprocessor” complex containing the Drosha endonuclease and its partner protein, DGCR8. To investigate the roles of DGCR8 in this and other cellular pathways, the researchers established a human embryonic stem-cell line carrying a monoallelic DGCR8 mutation by the CRISPR-Cas9 system. This mutation results in only a modest effect on the DGCR8 mRNA level but a significant decrease at the protein level. Self-renewal and trilineage differentiation capacity of stem cells are not affected but partial disturbance of the Microprocessor function could be revealed in pri-miRNA processing along the chromosome 19 miRNA cluster. The study demonstrates that such a mutant stem cell line is a good model to investigate not only miRNA-related but also other “noncanonical” functions of the DGCR8 protein, as well as the ”DiGeorge syndrome”, a human disease with one mutant chromosomal region containing the DGCR8 gene.