Regulation of nuclear-cytoplasmic partitioning by the lin-28 - lin-46 pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression in C. elegans .
| Autor: | Ilbay O; Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA., Ambros V; Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA victor.ambros@umassmed.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Development (Cambridge, England) [Development] 2019 Nov 06; Vol. 146 (21). Date of Electronic Publication: 2019 Nov 06. |
| DOI: | 10.1242/dev.183111 |
| Abstrakt: | MicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. In Caenorhabditis elegans , the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2)-stage cell fates, and the let-7 family microRNAs temporally downregulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel to let-7 -family microRNAs, the conserved RNA-binding protein LIN-28 and its downstream gene lin-46 also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how the lin-28-lin-46 pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by the lin-28-lin-46 pathway is independent of the let-7 / lin-4 microRNA complementary sites (LCSs) in the hbl-1 3'UTR, and involves stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that robust progression from L2 to L3 cell fates depends on the combination of two distinct modes of HBL-1 downregulation: decreased synthesis of HBL-1 via let-7 -family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of the lin-28 - lin-46 pathway. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2019. Published by The Company of Biologists Ltd.) |
| Databáze: | MEDLINE |
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