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
Ambros, Victor R.
UMass Chan AffiliationsProgram in Molecular Medicine
Document TypeJournal Article
Amino Acids, Peptides, and Proteins
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractMicroRNAs 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.
Ilbay O, Ambros V. 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. Development. 2019 Nov 6;146(21):dev183111. doi: 10.1242/dev.183111. PMID: 31597658; PMCID: PMC6857590. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44408
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