title: The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans.
abstract: The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during the oocyte-to-embryo transition. To understand how the oocyte reprogramming potential is controlled, we sought Caenorhabditis elegans mutants in which embryonic transcription is initiated precociously in germ cells. This screen identified LIN-41, a TRIM-NHL protein and a component of the somatic heterochronic pathway, as a temporal regulator of pluripotency in the germline. We found that LIN-41 is expressed in the cytoplasm of developing oocytes, which, in lin-41 mutants, acquire pluripotent characteristics of embryonic cells and form teratomas. To understand LIN-41 function in the germline, we conducted structure-function studies. In contrast to other TRIM-NHL proteins, we found that LIN-41 is unlikely to function as an E3 ubiquitin ligase. Similar to other TRIM-NHL proteins, the somatic function of LIN-41 is thought to involve mRNA regulation. Surprisingly, we found that mutations predicted to disrupt the association of LIN-41 with mRNA, which otherwise compromise LIN-41 function in the heterochronic pathway in the soma, have only minor effects in the germline. Similarly, LIN-41-mediated repression of a key somatic mRNA target is dispensable for the germline function. Thus, LIN-41 appears to function in the germline and the soma via different molecular mechanisms. These studies provide the first insight into the mechanism inhibiting the onset of embryonic differentiation in developing oocytes, which is required to ensure a successful transition between generations.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tocchini
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Keusch
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Miller
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Finger
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gut
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stadler
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ciosk
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D009154:Mutation; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C410586:LIN-41 protein, C elegans; D012333:RNA, Messenger; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases