title: Period homolog LIN-42 regulates miRNA transcription to impact developmental timing.
abstract: Two recent studies by Van Wynsberghe et al. and Perales et al. in the nematode C. elegans have demonstrated a new function of the Period protein homolog LIN-42 in negatively regulating microRNA (miRNA) biogenesis at the transcriptional level. LIN-42 is a complex gene with 4 isoforms and multiple functions including the regulation of molting, developmental timing and entry into dauer. These recent studies uncover an additional function of LIN-42 as a negative regulator of miRNA transcription. Approximately 95% of miRNAs present in eggs and 33% of miRNAs present in L4 stage worms were upregulated in lin-42 mutant worms relative to wild type (WT) worms, suggesting that LIN-42 globally regulates miRNA biogenesis. Expression from both a let-7 miRNA and a lin-4 miRNA transcriptional reporter were enhanced in the absence of lin-42. Additionally, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) of late larval stage worms showed that LIN-42 bound the let-7 promoter, suggesting that LIN-42 affects mature miRNA levels by inhibiting their transcription. In addition to miRNAs, LIN-42 also predominantly bound to the promoters of many diverse protein-coding genes. These findings support the action of LIN-42 at multiple points within the heterochronic and other regulatory pathways to impact a multitude of functions including developmental timing.
authors.affiliation: Department of Biology; Colgate University ; Hamilton, NY USA.
authors.forename: Priscilla M
authors.initials: PM
authors.lastname: Van Wynsberghe
authors.affiliation: Division of Biology; University of California, San Diego ; La Jolla, CA USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Pasquinelli
keywords: C. elegans; LIN-42; Period; developmental timing; heterochronic; let-7; miRNA