biostudies-literatureXu ZNational Science Foundation of ChinaShanghaiTech UniversityNIH HHSRP89903https://www.ebi.ac.uk/biostudies/studies/S-EPMC11223767biostudies-literatureUnknown12Precise 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> eLifeEssential function of transmembrane transcription factor MYRF in promoting transcription of miRNA <i>lin-4</i> during <i>C. elegans</i> development.PMC1122376731900397P40 OD010440Qi YBWang ZXu ZWang LfalseEssential function of transmembrane transcription factor MYRF in promoting transcription of miRNA <i>lin-4</i> during <i>C. elegans</i> development.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> 2024-01-01T00:00:00Z2024 Jul2025-04-04T23:54:35.716Z2025-04-04T23:54:35.716ZS-EPMC112237673896341110.7554/eLife.89903