Extragenic suppressors of a dominant masculinizing her‐1 mutation in C. elegans identify two new genes that affect sex determination in different ways

Abstract

The her-1 regulatory switch gene in C. elegans sex determination is normally active in XO animals, resulting in male development, and inactive in XX animals, allowing hermaphrodite development. The her-1(n695gf) mutation results in the incomplete transformation of XX animals into phenotypic males. We describe four extragenic mutations that suppress the masculinized phenotype of her-1(n695gf) XX. They define two previously undescribed genes, sup-26 and sup-27. All four mutations exhibit semidominance of suppression and by themselves have no visible effects on sex determination in otherwise genotypically wild-type XX or XO animals. Analysis of interactions with mutations in the major sex-determining genes show that sup-26 and sup-27 influence sex determination in fundamentally different ways. sup-26 appears to act independently of her-1 to negatively modulate synthesis or function of tra-2 in both XX and XO animals. sup-27 may play a role in X-chromosome dosage compensation and influence sex determination indirectly.

A microRNA family exerts maternal control on sex determination inC. elegans

“…sup-26 encodes an RNA-binding protein (RBP) containing a Q-rich low complexity domain and two RNA recognition motifs ( Figure 5A). sup-26 was previously isolated in a screen for suppressors of the Egl phenotype of her-1(gf), and we confirmed this genetic interaction (Manser et al 2002) ( Figure S1). We also previously demonstrated that sup-26 is required for another aspect of the mir-35-41(nDf50) mutant phenotype: temperature-sensitive loss of fecundity (McJunkin and Ambros 2014).…”

“…We set out to define the complement of SUP-26 binding targets for two reasons. (1) Previous genetic and biochemical data support a role for SUP-26 in repressing tra-2 translation to regulate sex determination (Manser et al 2002;Mapes et al 2010). However, we observed that sup-26 was required for the change in her-1 abundance in mir-35-41 mutant embryos, suggesting SUP-26 may regulate additional targets upstream of tra-2.…”

Somatic sex determination in Caenorhabditis elegans is modulated by SUP-26 repression of tra-2 translation

“…Loss-of-function (lf) mutations in sup-26 are semidominant suppressors of the masculinization defect in her-1(n695gf) XX animals and can suppress other masculinization defects in the absence of her-1, indicating that sup-26 likely acts downstream of her-1 to affect somatic sex determination (28). We find that sup-26 encodes an RNA recognition motif (RRM) containing protein that is expressed widely in somatic tissues, regulates the level of the tra-2 protein in the soma through the TGEs in the tra-2 3′ UTR, and binds directly to TGEs in vitro.…”

“…sup-26(n1091) was isolated as a semidominant suppressor of the masculinized defect of her-1(n695gf) XX animals (Table S1) and mapped to a small genetic interval at approximately -3.2 genetic map units on linkage group (LG) III (28). To clone sup-26, fosmids covering this genetic interval were injected into sup-26(n1091); her-1(n695) animals and tested for restoration of the masculinized Tra phenotype (Fig.…”

Themir-35family links maternal germline sex to embryonic viability inC. elegans

“…We found that this aberrant upregulation of male-specific gene expression was driven by derepression of two mir-35-41 target genes encoding RNA binding proteins. One of these genes, , had previously been identified as a male-promoting modulator of the sex determination pathway (Manser et al 2002;Mapes et al 2010) while the other gene, NHL domain containing-2 (nhl-2), was not previously implicated in sex determination.…”