TY - JOUR T1 - <em>C. elegans</em> LIN-28 controls temporal cell-fate progression by regulating LIN-46 expression via the 5’UTR of <em>lin-46</em> mRNA JF - bioRxiv DO - 10.1101/697490 SP - 697490 AU - Orkan Ilbay AU - Charles Nelson AU - Victor Ambros Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/10/697490.abstract N2 - Human Lin28 is a conserved RNA-binding protein that promotes proliferation and pluripotency and can be oncogenic. Lin28 and C. elegans LIN-28 bind to precursor RNAs of the conserved, cellular differentiation-promoting, microRNA let-7 and inhibits production of mature let-7 microRNA. Lin28/LIN-28 also binds to and regulates many mRNAs in various cell types. However, the determinants and consequences of these LIN-28-mRNA interactions are not well understood. Here, we report that LIN-28 in C. elegans represses the expression of LIN-46, a downstream protein in the heterochronic pathway, via the 5’ UTR of the lin-46 mRNA. We show that both LIN-28 and the 5’UTR of lin-46 are required to prevent LIN-46 expression in the L1 and L2 stages, and that precocious LIN-46 expression is sufficient to skip L2 stage proliferative cell-fates, resulting in heterochronic defects similar to the ones observed in lin-28(0) animals. We propose that the lin-46 5’UTR mediates LIN-28 binding to and repression of the lin-46 mRNA. Our results demonstrate that precocious LIN-46 expression alone can account for lin-28(0) phenotypes, demonstrating the biological importance of regulation of individual target mRNAs by LIN-28. ER -