Essential Function of Membrane-Bound Transcription Factor MYRF in Promoting Transcription of miRNA lin-4 during C. elegans Development

Abstract

Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 plays a critical role in developmental timing. While lin-4’s downregulation of LIN-14 is well-established, the mechanisms behind lin-4 upregulation remain unknown. We demonstrate that the membrane-associated transcription factor MYRF-1 is necessary for lin-4 upregulation in late L1 stage. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. We show that MYRF-1 regulates lin-4 expression cell-autonomously and that hyperactive MYRF-1 can prematurely drive lin-4 expression in early L1 and embryos. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly acts on the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.