RRC ID 80733
Author Kinney B, Sahu S, Stec N, Hills-Muckey K, Adams DW, Wang J, Jaremko M, Joshua-Tor L, Keil W, Hammell CM.
Title A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development.
Journal Dev Cell
Abstract Development relies on the exquisite control of both the timing and the levels of gene expression to achieve robust developmental transitions. How cis- and trans-acting factors control both aspects simultaneously is unclear. We show that transcriptional pulses of the temporal patterning microRNA (miRNA) lin-4 are generated by two nuclear hormone receptors (NHRs) in C. elegans, NHR-85 and NHR-23, whose mammalian orthologs, Rev-Erb and ROR, function in the circadian clock. Although Rev-Erb and ROR antagonize each other to control once-daily transcription in mammals, NHR-85/NHR-23 heterodimers bind cooperatively to lin-4 regulatory elements to induce a single pulse of expression during each larval stage. Each pulse's timing, amplitude, and duration are dictated by the phased expression of these NHRs and the C. elegans Period ortholog, LIN-42, that binds to and represses NHR-85. Therefore, during nematode temporal patterning, an evolutionary rewiring of circadian clock components couples the timing of gene expression to the control of transcriptional dosage.
Volume 58(22)
Pages 2563-2579.e8
Published 2023-11-20
DOI 10.1016/j.devcel.2023.08.006
PII S1534-5807(23)00402-1
PMID 37643611
PMC PMC10840721
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Gene Expression Regulation, Developmental Gene Regulatory Networks Mammals / metabolism MicroRNAs* / genetics MicroRNAs* / metabolism Receptors, Cytoplasmic and Nuclear / metabolism Transcription Factors / genetics Transcription Factors / metabolism
C.elegans tm4063