Selected Results – Institute of Molecular Genetics of the Czech Academy of Sciences

piRNA and female fertility

The analysis of the piRNA mechanism in hamster germ cells has changed the view of the functioning of this mechanism in mammalian germ cells by showing, among other things, that piRNAs are also important for female fertility.

piRNAs are small RNAs, which contribute to genome defence in animal germ cells. The piRNA pathway recognizes and silences endogenous retroviruses and other parasitic mobile DNA sequences. Studies of piRNAs in mouse mutants suggested that mammalian piRNAs are nonessential for oocytes. However, analysis of hamsters, whose piRNA pathway is similar to other mammals including humans, showed that mammalian piRNAs are also essential for oocytes, while the mouse model evolved in a different way.

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Řez varletem třináctidenního křečka. — Cutting through the testicle of a 13-day old hamster. The circular formations are the seminiferous tubules where sperm development will take place in adulthood. In blue is the DNA, in red the protein in the supporting cells, and in green the sex cells, called spermatogonia, from which sperm will develop in the future. The testes of the mutant (top) almost lack the green-stained spermatogonia that are normally present in the testes (bottom).


Publication	Loubalova Z, Fulka H, Horvat F, Pasulka J, Malik R, Hirose M, Ogura A, and Svoboda P: Formation of spermatogonia and fertile oocytes in golden hamsters requires piRNAs. Nat Cell Biol 2021 23(9): 992-1001. [pubmed] [doi]
Contact	Petr Svoboda, (+420) 296 443 147, petr.svoboda@img.cas.cz
Cooperating subject	Atsuo Ogury Laboratory, RIKEN Institute, Japan

New protein – TSSC4

snRNP particles are the building blocks of a huge complex that catalyzes pre-mRNA splicing. In this study, we describe a novel protein that helps fold this complex.

Before a protein is synthetized, the information for its synthesis is first transcribed from DNA into an RNA molecule called pre-mRNA. However, only a small part of pre-mRNA contains the information for the protein, the rest must be removed in a process called RNA splicing. All steps during RNA splicing are carried out by molecular scissors – a huge complex containing 150 components. In this work, we described a new protein that assists the correct and rapid assembly of the molecular scissors.

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In our work we showed that TSSC4 (marked in red) is a protein that binds to unassembled subunits (marked in orange) and holds them together until the complex involved in RNA splicing (right) is formed. After RNA splicing is complete, TSSC4 re-binds and helps with the recycling of the subunits.


Publication	Klimešová K, Vojáčková J, Radivojević N, Vandermoere F, Bertrand E, Verheggen C, Staněk D: TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation. Nat Commun 2021 12(1): 3646. [pubmed] [doi]
Contact	David Staněk, (+420) 296 443 118, david.stanek@img.cas.cz
Cooperating subject	Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France Equipe labélisée Ligue Nationale Contre le Cancer, Montpellier, France Institut de Génomique Fonctionnelle, University of Montpellier, CNRS, INSERM, Montpellier, France

Meis family transcription factors

Research revealing the essential role of Meis family transcription factors as regulators of cell fate competence and providing mechanistic insight into gene regulatory networks in the retina.

Vision is a crucial sense of vertebrates. Genetic manipulation in mice allows addressing the role of individual genes in eye development, and given the conserved role of genes, implicate their function in humans as well. We show that in the developing mouse embryo, Meis transcription factors control complex gene regulatory networks responsible for the maintenance of progenitor cells and retina differentiation.

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(A) Schematic diagram of wild type and Meis1/Meis2-deficient (cKO) retina
(B) The proposed regulatory inputs of Meis transcription factors into gene expression programmes.
During retinal development, three spatially patterned domains are formed: the ciliary margin zone (CMZ), the optic disc (OD), and the region which contains retinal progenitor cells (RPCs). We show that Meis transcription factors maintain the RPC pool and suppress the expression of genes characteristic of the CMZ and the OD fates.


Publication	Dupacova N, Antosova B, Paces J, Kozmik Z: Meis homeobox genes control progenitor competence in the retina. Proc Natl Acad Sci U S A 2021 118(12). [pubmed] [doi]
Contact	Zbyněk Kozmik, (+420) 296 442 110, zbynek.kozmik@img.cas.cz