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PQN-59 antagonizes microRNA-mediated repression during post-embryonic temporal patterning and modulates translation and stress granule formation in C. elegans
- Source :
- PLoS Genetics, Vol 17, Iss 11, p e1009599 (2021), PLoS Genetics, 17 (11), PLoS Genetics, PLOS genetics, Vol. 17, No 11 (2021) P. e1009599
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- microRNAs (miRNAs) are potent regulators of gene expression that function in a variety of developmental and physiological processes by dampening the expression of their target genes at a post-transcriptional level. In many gene regulatory networks (GRNs), miRNAs function in a switch-like manner whereby their expression and activity elicit a transition from one stable pattern of gene expression to a distinct, equally stable pattern required to define a nascent cell fate. While the importance of miRNAs that function in this capacity are clear, we have less of an understanding of the cellular factors and mechanisms that ensure the robustness of this form of regulatory bistability. In a screen to identify suppressors of temporal patterning phenotypes that result from ineffective miRNA-mediated target repression, we identified pqn-59, an ortholog of human UBAP2L, as a novel factor that antagonizes the activities of multiple heterochronic miRNAs. Specifically, we find that depletion of pqn-59 can restore normal development in animals with reduced lin-4 and let-7-family miRNA activity. Importantly, inactivation of pqn-59 is not sufficient to bypass the requirement of these regulatory RNAs within the heterochronic GRN. The pqn-59 gene encodes an abundant, cytoplasmically-localized, unstructured protein that harbors three essential "prion-like"domains. These domains exhibit LLPS properties in vitro and normally function to limit PQN- 59 diffusion in the cytoplasm in vivo. Like human UBAP2L, PQN-59's localization becomes highly dynamic during stress conditions where it re-distributes to cytoplasmic stress granules and is important for their formation. Proteomic analysis of PQN-59 complexes from embryonic extracts indicates that PQN-59 and human UBAP2L interact with orthologous cellular components involved in RNA metabolism and promoting protein translation and that PQN-59 additionally interacts with proteins involved in transcription and intracellular transport. Finally, we demonstrate that pqn-59 depletion reduces protein translation and also results in the stabilization of several mature miRNAs (including those involved in temporal patterning). These data suggest that PQN-59 may ensure the bistability of some GRNs that require miRNA functions by promoting miRNA turnover and, like UBAP2L, enhancing protein translation.<br />PLoS Genetics, 17 (11)<br />ISSN:1553-7390<br />ISSN:1553-7404
- Subjects :
- Cancer Research
Nematoda
Gene regulatory network
QH426-470
Biochemistry
RNA interference
Gene expression
RNA Processing, Post-Transcriptional
Genetics (clinical)
Microscopy
0303 health sciences
030302 biochemistry & molecular biology
Intracellular Signaling Peptides and Proteins
Eukaryota
Light Microscopy
Translation (biology)
Animal Models
Stress Granules
Cell biology
Nucleic acids
Phenotypes
Genetic interference
Experimental Organism Systems
Epigenetics
Research Article
Prions
Fluorescence Recovery after Photobleaching
Cell fate determination
Biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Stress granule
microRNA
Genetics
Animals
ddc:612
Non-coding RNA
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
Gene
Alleles
Ecology, Evolution, Behavior and Systematics
Body Patterning
030304 developmental biology
Natural antisense transcripts
Biology and life sciences
Organisms
Proteins
Invertebrates
Gene regulation
MicroRNAs
Gene Expression Regulation
Genetic Loci
Protein Biosynthesis
Animal Studies
Caenorhabditis
RNA
Protein Translation
Carrier Proteins
Zoology
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 17
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....bad2d1e43cf433bdb8641df92f077765