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RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification

Hutchins, Erica J. and Gandhi, Shashank and Chacon, Jose and Piacentino, Michael L. and Bronner, Marianne E. (2020) RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification. . (Unpublished)

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While neural crest development is known to be transcriptionally controlled via sequential activation of gene regulatory networks (GRNs), recent evidence increasingly implicates a role for post-transcriptional regulation in modulating the output of these regulatory circuits. Using available single cell RNA-sequencing datasets from avian embryos to identify potential post-transcriptional regulators, we found that Elavl1, which encodes for an RNA-binding protein with roles in transcript stability, was enriched in the premigratory cranial neural crest. Perturbation of Elavl1 resulted in premature neural crest delamination from the neural tube as well as significant reduction in transcripts associated with the neural crest specification GRN, phenotypes that are also observed with downregulation of the canonical Wnt inhibitor Draxin. That Draxin is the primary target for stabilization by Elavl1 during cranial neural crest specification was shown by RNA-sequencing, RNA-immunoprecipitation, RNA decay measurement and proximity ligation assays, further supporting the idea that the downregulation of neural crest specifier expression upon Elavl1 knockdown was largely due to loss of Draxin. Importantly, exogenous Draxin rescued cranial neural crest specification defects observed with Elavl1 knockdown. Thus, Elavl1 plays a critical a role in the maintenance of cranial neural crest specification via Draxin mRNA stabilization. Together, these data highlight an important intersection of post-transcriptional regulation with modulation of the neural crest specification GRN.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper ItemJournal Article
Hutchins, Erica J.0000-0002-4316-0333
Gandhi, Shashank0000-0002-4081-4338
Chacon, Jose0000-0001-7965-3976
Piacentino, Michael L.0000-0003-1773-031X
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. Version 1 - October 14. 2020; Version 2 - July 27, 2022. We thank A. Collazo and G. Spigolon for imaging assistance at the Caltech Biological Imaging Facility; M. Schwarzkopf and G. Shin (Molecular Technologies) for HCR probe design; I. Antoshechkin of the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory for sequencing of RNA-seq libraries; S. Manohar for assistance with Axud1 3’-RACE; and G. da Silva Pescador and R. Galton for assistance with pilot experiments. This work was supported by the National Institutes of Health [R01DE027538 and R01DE027568 to M.E.B; K99DE028592 to E.J.H; K99DE029240 to M.L.P.], the California State University—Northridge BUILD PODER program [TL4GM118977], and the Amgen Foundation Caltech Amgen Scholars Program [J.C.]. The authors declare no competing interests. Data Availability: RNA-sequencing datasets have been deposited on NCBI under the accession number PRJNA861325. The 3’ untranslated region (UTR) sequence for Axud1 has been deposited to GenBank under accession number ON920861.
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California State University, NorthridgeUNSPECIFIED
Amgen Scholars ProgramUNSPECIFIED
Record Number:CaltechAUTHORS:20201015-152733431
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Official Citation:RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification. Erica J. Hutchins, Shashank Gandhi, Jose Chacon, Michael L. Piacentino, Marianne E. Bronner. bioRxiv 2020.10.14.338715; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106093
Deposited By: George Porter
Deposited On:16 Oct 2020 14:41
Last Modified:22 Mar 2023 22:55

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