Essential Function of Transmembrane Transcription Factor MYRF in Promoting Transcription of miRNAlin-4duringC. elegansDevelopment

Abstract

AbstractPrecise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. InC. elegans, the microRNAlin-4critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation oflin-4expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary forlin-4activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide withlin-4expression timing. MYRF-1 regulateslin-4expression cell-autonomously and hyperactive MYRF-1 can prematurely drivelin-4expression in embryos and young first-stage larvae. The tandemlin-4promoter DNA recruits MYRF-1GFPto form visible loci in the nucleus, suggesting that MYRF-1 directly binds to thelin-4promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator oflin-4expression.