The Doubletime HomologKIN-20Mainly Regulateslet-7Independently of Its Effects on the Period HomologLIN-42inCaenorhabditis elegans

Abstract

The Caenorhabditis elegans (C. elegans) heterochronic pathway, which regulates developmental timing, is thought to be an ancestral form of the circadian clock in other organisms. An essential member of this clock is the Period protein whose homolog, lin-42, in C. elegans is an important heterochronic gene. LIN-42 functions as a transcriptional repressor of multiple genes including the conserved lin-4 and let-7 microRNAs. Like other Period proteins, levels of LIN-42 oscillate throughout development. In other organisms this cycling is controlled in part by phosphorylation. KIN-20 is the C. elegans homolog of the Drosophila Period protein kinase Doubletime. Worms containing a large deletion in kin-20 have a significantly smaller brood size and develop slower than wild type C. elegans. Here we analyze the effect of kin-20 on lin-42 phenotypes and microRNA expression. We find that kin-20 RNAi enhances loss-of-function lin-42 mutant phenotypes and that kin-20 mutant worms express lower levels of LIN-42. We also show that kin-20 is important for post-transcriptional regulation of mature let-7 and lin-4 microRNA expression. In addition, the increased level of let-7 found in lin-42(n1089) mutant worms is not maintained after kin-20 RNAi treatment. Instead, let-7 is further repressed when levels of kin-20 and lin-42 are both decreased. Altogether these results suggest that though kin-20 regulates lin-42 and let-7 microRNA, it mainly affects let-7 microRNA expression independently of lin-42. These findings further our understanding of the mechanisms by which these conserved circadian rhythmic genes interact to ultimately regulate rhythmic processes, developmental timing and microRNA biogenesis in C. elegans.

Casein Kinase 1δ Stabilizes Mature Axons by Inhibiting Transcription Termination of Ankyrin

“…At the L2 stage, KIN-20 is also highly expressed in the nuclei of epidermal cells and is visible in the nuclei of motor neurons (Figure S3H). Expression tends to peak at the end of each larval stage, consistent with expression of other heterochronic genes (Rhodehouse et al, 2018). In the L4 stage, kin-20 is localized to the nucleus of all cell types (Figure S3B) and at adherens junctions in the spermatheca (Figure S3C).…”

“…The CK1d ortholog in Drosophila was isolated as doubletime, a mutant with defects in circadian rhythms (Kloss et al, 1998;Price et al, 1998). A conserved pathway comprising doubletime, period, and timeless regulate circadian rhythms in most animals (Young and Kay, 2001) and regulate heterochronic gene expression in nematodes (Rhodehouse et al, 2018;Temmerman et al, 2011;Tennessen et al, 2006Tennessen et al, , 2010. In nematodes, the knockdown of kin-20 by RNA interference promoted the formation of precocious, stage-specific cuticle structures called alae (Banerjee et al, 2005;Rhodehouse et al, 2018).…”

Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans

“…The shared GO terms stem from different sets of genes being expressed at the equivalent stage and region but are used for a similar function. The shared GO term “developmental processes” in S. carpocapsae young females represents 113 genes which encompass pathways such as Wnt signaling ( siah-1, kin-20 ) 58,59 , and several genes categorized in angiogenesis ( jnk-1, sem-5, mpk-1, let-60, pxl-1 ) 60–64 . The genes that fell in the category of angiogenesis are important for C. elegans vulva development 65 .…”

“…The genes that fell in the category of angiogenesis are important for C. elegans vulva development 65 . The Wnt signaling genes are known to be part of linker cell type death 66 ( siah-1 ) and seam cell development 58 ( kin-20 ). On the other hand, we found 196 genes in C. elegans young hermaphrodite for the “developmental processes” term.…”

Regulation of the circadian clock inC. elegansby clock gene homologskin-20andlin-42

“…In the complete absence of lin-42 , hypodermal seam cells, vulval precursor cells, and the migration of sex myoblasts all develop precociously [17]. lin-42 mRNA levels oscillate during each of the four molting cycles of postembryonic development (approximately 8-10 h at 25°C) [16] regulating developmental timing and entrance into an alternative dauer larval stage [12, 15, 17] likely through gene expression modulation [18–21]. The kin-20 gene also encodes seven isoforms (isoforms a-g), and it is expressed in seam cells and neurons [8].…”