Dose-Dependent Effects of GLD-2 and GLD-1 on Germline Differentiation and Dedifferentiation in the Absence of PUF-8

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Youngyong,O’Rourke,Samuel,Taki,Faten A.,Alfhili,Mohammad A.,Hee Lee,Myon Park (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: PUMILIO/FBF (PUF) proteins have a conserved function in stem cell regulation.Caenorhabditis elegans PUF-8 protein inhibits the translation of target mRNAs byinteracting with PUF binding element (PBE) in the 30 untranslated region (30 UTR). Inthis work, an in silico analysis has identified gld-2 [a poly(A) polymerase] as a putativePUF-8 target. Biochemical and reporter analyses showed that PUF-8 specifically bindsto a PBE in gld-2 30 UTR and represses a GFP reporter gene carrying gld-2 30 UTRin the C. elegans mitotic germ cells. GLD-2 enhances meiotic entry at least in part byactivating GLD-1 (a KH motif-containing RNA-binding protein). Our genetic analysesalso demonstrated that heterozygous gld-2(+/−) gld-1(+/−) genes in the absenceof PUF-8 are competent for meiotic entry (early differentiation), but haplo-insufficientfor the meiotic division (terminal differentiation) of spermatocytes. Indeed, the arrestedspermatocytes return to mitotic cells via dedifferentiation, which results in germlinetumors. Since these regulators are broadly conserved, we thus suggest that similarmolecular mechanisms may control differentiation, dedifferentiation, and tumorigenesisin other organisms, including humans.

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Language: English

Date: 2020

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