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Circadian rhythm orthologs drive pulses of heterochronic miRNA transcription in C. elegans

By Brian Kinney, Shubham Sahu, Natalia Stec, Kelly Hills-Muckey, Dexter Adams, Jing Wang, Matt Jaremako, Leemor Joshua-Tor, Wolfgang Keil, Christopher M Hammell

Posted 26 Sep 2022
bioRxiv DOI: 10.1101/2022.09.26.509508

The C. elegans transcriptome exhibits reproducible, periodic patterns that are phase-locked with features of the larval molting cycle, but the gene regulatory networks underlying this interdependency are unknown. We show here that repeated transcriptional pulses of the lin-4 temporal patterning miRNA are generated by cooperative binding between the C. elegans orthologs of master circadian regulators Rev-Erb and ROR to elements upstream of the lin-4 gene. Remarkably, the precise timing and length of lin-4 transcriptional pulses are dictated by the phased overlap of NHR-85Rev-Erb and NHR-23ROR temporal expression patterns. We also demonstrate that LIN-42Period functions in a similar capacity to its circadian orthologs to negatively regulate periodic transcription but does so by limiting the duration of NHR-85Rev-Erb/NHR-23ROR cooperative activity at the lin-4 gene.

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