The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA

Abstract

Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its paralogs, including mir-84, control the timing of stage-specific developmental events. To identify factors required for the activity of mir-84 and possibly other miRNAs, we screened for mutations that suppress the developmental defects caused by overexpression of mir-84. Mutations in the somi-1 gene prevent these defects without affecting the expression level of mir-84. Loss of somi-1 also causes phenotypes similar to deletion of mir-84, showing that somi-1 is necessary for the normal function of this miRNA. somi-1 encodes a zinc finger protein that localizes to nuclear foci and binds the promoters of let-60/RAS, lin-14, and lin-28, genes that may be targeted by mir-84 and similar miRNAs. Genetic evidence shows that somi-1 inhibits lin-14 and induction of the vulval precursors by the let-60/RAS pathway. Proteomic and genetic screens identified conserved chromatin-remodeling and homeodomain transcription factor complexes that work with somi-1 to regulate differentiation. Our results suggest that somi-1 coordinates a nuclear response that complements the activity of mir-84.

Transcriptional regulation of Caenorhabditis elegansFOXO/DAF-16 modulates lifespan

“…In C. elegans , SWI/SNF is required for asymmetric cell division [51] and differentiation [52]. Prior to the L4 stage, Pdaf-16d/f::gfp expression was unaffected by swsn-1 RNAi (Figure 5A,B).…”

Multiple small RNA pathways regulate the silencing of repeated and foreign genes in C. elegans

“…The genes mostly frequently (up to 17 times) found coexpressed with the genes identified in the screen (Supplemental Table 4) include two Argonautes, transcription factors, chromatin factors, splicing factors, nucleoporins, and RNA-binding proteins. For example, the attf-2 AT hook transcription factor is coregulated with cluster 2 and 3 genes and the Zn finger transcription factor somi-1 that regulates a nuclear response to the miRNA mir-84 (Hayes et al 2011) with cluster 4 genes.…”

Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits DuringCaenorhabditis elegansDevelopment

“…The zinc-finger protein SOMI-1 binds the promoter of let-60 to repress its gene expression and therefore inhibit the induction of the VPCs (Hayes et al 2011). Hayes and coworkers described that HAM-3 cooperates with SOMI-1 in the differentiation of hypodermal cells (Hayes et al 2011). Therefore, a direct inhibitory action of HAM-3, and maybe of SWSN-2.2, on the promoter of let-60 could explain their role in repressing vulva induction.…”

“…The vulva phenotype was determined at young adult stage under the dissection microscope (n≥278 in A) (n≥154 in B). lin-15A(RNAi) and somi-1(RNAi) served as positive controls for ectopic induction of the vulval cells (Hayes, Riedel & Ruvkun, 2011;Ceol et al, 2006). Error bars indicate the standard deviation between two independent experiments.…”

“…ham-3 and swsn-2.2 exhibit RNA interference (RNAi) phenotypes in vulva development and fertility, present a synthetic genetic interaction with lin-35/Rb (Cui et al 2004;Ceron et al 2007), and are implicated in somatic gonad development (Large and Mathies 2014). In addition to these common functions, ham-3 has been described to be involved in neuronal specification and in the transcriptional regulation of specific microRNAs (Hayes et al 2011;Weinberg et al 2013). Differently from ham-3, loss of swsn-2.2 produces Emb (embryonic lethality) and Psa (phasmid socket absent; specific cells acquiring hypodermal fate instead of the neuronal fate) phenotypes at high penetrance (Sawa et al 2000;Large and Mathies 2014).…”