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

Abstract

Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In <i>C. elegans</i>, the microRNA <i>lin-4</i> critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of <i>lin-4</i> expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for <i>lin-4</i> activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with <i>lin-4</i> expression timing. MYRF-1 regulates <i>lin-4</i> expression cell-autonomously and hyperactive MYRF-1 can prematurely drive <i>lin-4</i> expression in embryos and young first-stage larvae. The tandem <i>lin-4</i> promoter DNA recruits MYRF-1^GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the <i>lin-4</i> promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of <i>lin-4</i> expression.