dc.contributor.author | Ochs, Matthew E. | |
dc.contributor.author | McWhirter, Rebecca M. | |
dc.contributor.author | Unckless, Robert L. | |
dc.contributor.author | Miller, David M., III | |
dc.contributor.author | Lundquist, Erik A. | |
dc.date.accessioned | 2022-02-08T16:04:06Z | |
dc.date.available | 2022-02-08T16:04:06Z | |
dc.date.issued | 2022-01-06 | |
dc.identifier.citation | Ochs, M.E., McWhirter, R.M., Unckless, R.L. et al. Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration. BMC Genomics 23, 13 (2022). https://doi.org/10.1186/s12864-021-08217-6 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32503 | |
dc.description.abstract | Migration of neuroblasts and neurons from their birthplace is central to the formation of neural circuits and networks. ETR-1 is the Caenorhabditis elegans homolog of the CELF1 (CUGBP, ELAV-like family 1) RNA-processing factor involved in neuromuscular disorders. etr-1 regulates body wall muscle differentiation. Our previous work showed that etr-1 in muscle has a non-autonomous role in neuronal migration, suggesting that ETR-1 is involved in the production of a signal emanating from body wall muscle that controls neuroblast migration and that interacts with Wnt signaling. etr-1 is extensively alternatively-spliced, and we identified the viable etr-1(lq61) mutant, caused by a stop codon in alternatively-spliced exon 8 and only affecting etr-1 isoforms containing exon 8. We took advantage of viable etr-1(lq61) to identify potential RNA targets of ETR-1 in body wall muscle using a combination of fluorescence activated cell sorting (FACS) of body wall muscles from wild-type and etr-1(lq61) and subsequent RNA-seq. This analysis revealed genes whose splicing and transcript levels were controlled by ETR-1 exon 8 isoforms, and represented a broad spectrum of genes involved in muscle differentiation, myofilament lattice structure, and physiology. Genes with transcripts underrepresented in etr-1(lq61) included those involved in ribosome function and translation, similar to potential CELF1 targets identified in chick cardiomyocytes. This suggests that at least some targets of ETR-1 might be conserved in vertebrates, and that ETR-1 might generally stimulate translation in muscles. As proof-of-principle, a functional analysis of a subset of ETR-1 targets revealed genes involved in AQR and PQR neuronal migration. One such gene, lev-11/tropomyosin, requires ETR-1 for alternative splicing, and another, unc-52/perlecan, requires ETR-1 for the production of long isoforms containing 3′ exons. In sum, these studies identified gene targets of ETR-1/CELF1 in muscles, which included genes involved in muscle development and physiology, and genes with novel roles in neuronal migration. | en_US |
dc.publisher | BMC | en_US |
dc.rights | © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Ochs, Matthew E. | |
kusw.kuauthor | Unckless, Robert L. | |
kusw.kuauthor | Lundquist, Erik A. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1186/s12864-021-08217-6 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC8734324 | en_US |
dc.rights.accessrights | openAccess | en_US |