A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development

Kinney, Brian, Sahu, Shubham, Stec, Natalia, Hills-Muckey, Kelly, Adams, Dexter W, Wang, Jing, Jaremko, Matt, Joshua-Tor, Leemor, Keil, Wolfgang, Hammell, Christopher M (August 2023) A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development. Developmental Cell. S1534-5807(23)00402. ISSN 1534-5807

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.

Item Type:	Paper
Subjects:	bioinformatics organism description > animal > C elegans bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal neurobiology > neuroscience > circadian rhythm bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA neurobiology neurobiology > neuroscience bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Kinney, Brian A. Stec, Natalia Hills-Muckey, Kelly Wang, Jing Jaremko, Matt Joshua-Tor, Leemor Hammell, Christopher M. Adams, Dexter
Communities:	CSHL labs > Hammell C. lab CSHL labs > Joshua-Tor lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	22 August 2023
Date Deposited:	19 Sep 2023 14:53
Last Modified:	11 Apr 2024 13:36
PMCID:	PMC10840721
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40906

Actions (login required)

Administrator's edit/view item