TRIM-NHL protein, NHL-2, modulates cell fate choices in the C. elegans germ line

• Published in: Developmental biology 2022-11, Vol.491, p.43-55
• Main Authors: Brenner, John L., Jyo, Erin M., Mohammad, Ariz, Fox, Paul, Jones, Vovanti, Mardis, Elaine, Schedl, Tim, Maine, Eleanor M.
• Format: Article
• Language: English
• Subjects: Animals; Argonaute Proteins - metabolism; C. elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Carrier Proteins - metabolism; Germ Cells - metabolism; Germline; GLP-1/Notch signaling; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Male; NHL-2; Receptors, Notch - metabolism; Repressor Proteins - metabolism; RNA - metabolism; RNA Nucleotidyltransferases - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Stem cell fate; Transcription Factors - metabolism; TRIM-NHL proteins; Tripartite Motif Proteins - metabolism
• ISSN: 0012-1606; 1095-564X; 1095-564X
• DOI: 10.1016/j.ydbio.2022.08.010

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that limit the stem cell fate and/or promote the meiotic fate. Here, we show that sog-10 is allelic to nhl-2. NHL-2 is a member of the conserved TRIM-NHL protein family whose members can bind RNA and ubiquitinate protein substrates. We show that NHL-2 acts, at least in part, by inhibiting the expression of PUF-3 and PUF-11 translational repressor proteins that promote the stem cell fate. Two other negative regulators of stem cell fate, CGH-1 (conserved germline helicase) and ALG-5 (Argonaute protein), may work with NHL-2 to modulate the stem cell population. In addition, NHL-2 activity promotes the male germ cell fate in XX animals. [Display omitted] •C. elegans sog-10 encodes a TRIM-NHL protein, NHL-2.•nhl-2(lf) suppresses reduced GLP-1/Notch and enhances ectopic GLP-1 in the germline.•NHL-2 promotes meiotic entry/inhibits the germline stem cell fate.•NHL-2 limits PUF-3 and PUF-11 abundance to promote meiotic entry.•ALG-5 Argonaute and CGH-1 helicase promote meiotic entry/inhibit stem cell fate.