PUBLICATION

Pumilio response and AU-rich elements drive rapid decay of Pnrc2-regulated cyclic gene transcripts

Authors
Tietz, K.T., Gallagher, T.L., Mannings, M.C., Morrow, Z.T., Derr, N.L., Amacher, S.L.
ID
ZDB-PUB-210106-36
Date
2020
Source
Developmental Biology   462: 129-140 (Journal)
Registered Authors
Amacher, Sharon, Derr, Nicolas, Gallagher, Thomas, Tietz, Kiel
Keywords
3′UTR, ARE, Hes/her, PRE, Somitogenesis, deltaC
MeSH Terms
  • Biological Clocks/genetics
  • Animals
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism
  • 3' Untranslated Regions
  • RNA Stability/genetics
  • RNA Stability/physiology*
  • Endoribonucleases/genetics
  • Endoribonucleases/metabolism
  • Mesoderm/embryology
  • Body Patterning/genetics
  • Gene Expression Regulation, Developmental
  • Embryonic Development
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
  • Zebrafish/embryology
  • Somites/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/genetics*
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Transcription Factors/metabolism
  • Trans-Activators/genetics*
  • Trans-Activators/metabolism*
  • Receptors, Cytoplasmic and Nuclear/genetics
(all 25)
PubMed
32246943 Full text @ Dev. Biol.
Abstract
Vertebrate segmentation is regulated by the segmentation clock, a biological oscillator that controls periodic formation of somites, or embryonic segments, which give rise to many mesodermal tissue types. This molecular oscillator generates cyclic gene expression with the same periodicity as somite formation in the presomitic mesoderm (PSM), an area of mesenchymal cells that give rise to mature somites. Molecular components of the clock include the Hes/her family of genes that encode transcriptional repressors, but additional genes cycle. Cyclic gene transcripts are cleared rapidly, and clearance depends upon the pnrc2 (proline-rich nuclear receptor co-activator 2) gene that encodes an mRNA decay adaptor. Previously, we showed that the her1 3'UTR confers instability to otherwise stable transcripts in a Pnrc2-dependent manner, however, the molecular mechanism(s) by which cyclic gene transcripts are cleared remained largely unknown. To identify features of the her1 3'UTR that are critical for Pnrc2-mediated decay, we developed an array of transgenic inducible reporter lines carrying different regions of the 3'UTR. We find that the terminal 179 nucleotides (nts) of the her1 3'UTR are necessary and sufficient to confer rapid instability. Additionally, we show that the 3'UTR of another cyclic gene, deltaC (dlc), also confers Pnrc2-dependent instability. Motif analysis reveals that both her1 and dlc 3'UTRs contain terminally-located Pumilio response elements (PREs) and AU-rich elements (AREs), and we show that the PRE and ARE in the last 179 ​nts of the her1 3'UTR drive rapid turnover of reporter mRNA. Finally, we show that mutation of Pnrc2 residues and domains that are known to facilitate interaction of human PNRC2 with decay factors DCP1A and UPF1 reduce the ability of Pnrc2 to restore normal cyclic gene expression in pnrc2 mutant embryos. Our findings suggest that Pnrc2 interacts with decay machinery components and cooperates with Pumilio (Pum) proteins and ARE-binding proteins to promote rapid turnover of cyclic gene transcripts during somitogenesis.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
oz22
    		Small Deletion
    oz44TgTransgenic Insertion
      oz45TgTransgenic Insertion
        oz46TgTransgenic Insertion
          oz47TgTransgenic Insertion
            oz48TgTransgenic Insertion
              oz50TgTransgenic Insertion
                oz51TgTransgenic Insertion
                  oz54TgTransgenic Insertion
                    oz55TgTransgenic Insertion
                      1 - 10 of 36
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab2-dlcmonoclonal
                        		IgG2aMouse
                        1 - 1 of 1
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        VenusEFGVenus
                        1 - 1 of 1
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                        Mapping
                        No data available
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                        Citation
                        Tietz, K.T., Gallagher, T.L., Mannings, M.C., Morrow, Z.T., Derr, N.L., Amacher, S.L. (2020) Pumilio response and AU-rich elements drive rapid decay of Pnrc2-regulated cyclic gene transcripts. Developmental Biology. 462:129-140.