A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development

A conserved chronobiological complex timesC. elegansdevelopment

“…While lin-42(n1089) removes the sequence of the PAS domains, it also results in a truncation of lin-42b and removal of part of the lin-42a promoter sequence (Tennessen et al , 2006; Monsalve et al , 2011). The n1089 phenotype could reflect loss of the PAS domains combined with potential reduction in expression of other elements such as the C-terminal tail or an NHR-85 interaction site (Kinney et al , 2023).…”

“…These findings agree with previous genetic data that suggested independent functions of lin-42 and kin-20 in regulating the expression of the heterochronic let-7 microRNA (Rhodehouse et al , 2018). A recent study on LIN-42’s function in regulating another heterochronic miRNA, lin-4 , indicated that physical interaction with the NHR-85 transcription factor may support LIN-42’s activity in this process, and perhaps the heterochronic pathway more generally (Kinney et al , 2023). Relatively mild effects upon nhr-85 deletion, and LIN-42’s ability to interact with additional transcription factors in a yeast two-hybrid assay suggest that additional functionally relevant interactions partners remain to be identified.…”

“…The components and wiring of the clock that controls rhythmic molting is only beginning to be elucidated, and it appears that some of the main components may differ from that of the circadian clock (Meeuse et al , 2023). Moreover, examination of factors that are conserved between the heterochronic timer and the circadian clock e.g., LIN-42/PER, NHR-23/RORa, and NHR-85/REV-ERB, suggested a different wiring among them (Kinney et al , 2023; Rhodehouse et al , 2018). The LIN-42-KIN-20 complex uncovered here is thus the first conserved module identified between the circadian clock and the nematode molting timer.…”

“…In a yeast two-hybrid assay, LIN-42 was shown to be capable of binding to numerous transcription factors. Although the functional relevance of such binding for molting has remained unexplored, LIN-42 binding to the REV-ERB orthologue NHR-85 appears important for robust periodic transcription of the heterochronic lin-4 miRNA (Kinney et al , 2023). Finally, loss of KIN-20, the C. elegans orthologue of CK1δ/ε, replicates some heterochronic phenotypes of lin-42 mutation and slows development (Banerjee et al , 2005), but its heterochronic functions were argued not to involve LIN-42 (Rhodehouse et al , 2018), and it is unknown whether KIN-20 is required for rhythmic molting.…”

Essential function of transmembrane transcription factor MYRF in promoting transcription of miRNA lin-4 during C. elegans development

“…The periodic activation of lin-4 transcription is likely driven by poorly understood oscillation gene regulatory circuits, some of which include C. elegans orthologs of human circadian clock genes ( Hendriks et al, 2014 ; McCulloch and Rougvie, 2014 ; Meeuse et al, 2020 ; Perales et al, 2014 ; Tsiairis and Großhans, 2021 ; Van Wynsberghe et al, 2014 ). Recent work has begun to reveal the regulation mechanisms underlying oscillating lin-4 transcription ( Kinney et al, 2023 ; Perales et al, 2014 ; Stec et al, 2021 ). BLMP-1/PRDM1 functions as a nutrient-stimulated priming factor to decompact the lin-4 locus and boost the amplitude of lin-4 oscillation ( Stec et al, 2021 ).…”