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Developmental roles of DDX3 helicase LAF-1

Germ cells are a pool of cells that serve as a link between generations. These cells are separated from the somatic cells by specialized type of cytoplasm, called the germ plasm. Germ plasm contains, membraneless, electron dense subcellular structures, termed germplasm granules that contain numerous components of mRNA metabolism pathway. One of the most prominent protein families, commonly found in germplasm granules are DEAD-box helicases. While this protein family is currently heavily investigated, surprisingly little is known about their functions in germ plasm granules and the mechanisms of their association with the granules.
This work identified novel biological and molecular roles of C. elegans’ LAF-1 in both somatic and germ cells. It reveals strong dependency of animal’s somatic, embryonic and post-embryonic development on LAF-1 activity, resulting in high penetrance developmental arrest phenotype. Moreover, this work documents requirement of LAF-1 for the fertility of the animal. Analysis of germ cells in the absence of LAF-1 activity reveals multilayered defects occurring at all stages of germ cell development and maturation. LAF-1 appears to be involved in the maintenance of proliferating potential of the germline stem cell pool and loss of LAF-1 significantly expands the region occupied by mitotic cells. Furthermore, loss of LAF-1 significantly affects expression of GLD-1, REC-8 and H3-S10P, implying that mitosis-to-meiosis boundary cannot be established correctly in the absence of LAF-1. This work solidifies previous conclusions that LAF-1 is a component of P granules, both in the adult germ cells and embryonic germ cell precursors and reveals that LAF-1 is required for correct assembly and dynamic behavior of P granules. Intrinsically disordered regions present in LAF-1 are indispensable for LAF-1’s association with P granules and its role in recruiting granule components. Lastly, LAF-1 associates with RNPs containing cytoplasmic polyA polymerases, indicating that LAF-1 might be involved in translational regulation. Altogether, the collected data describes biological functions of LAF-1 and elucidates the molecular mechanisms underlying these functions.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:74063
Date01 March 2021
CreatorsSzczepaniak, Krzysztof
ContributorsAnsorge-Schumacher, Marion, Jessberger, Rolf, Dahmann, Christian, Müller-Reichert, Thomas, Zierau, Oliver, Technische Universität Dresden
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relationinfo:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/Human Frontier Science Program/251841938//Evolution von Photorezeptoren bei Deuterostomia - neue Erkenntnisse durch Untersuchungen an Echinodermen und Enteropneusten

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