scholarly journals The predicted RNA-binding protein ETR-1/CELF1 acts in muscles to regulate neuroblast migration in Caenorhabditis elegans

2020 ◽  
Author(s):  
Matthew E. Ochs ◽  
Matthew P. Josephson ◽  
Erik A. Lundquist
Keyword(s):  
Neuronal Migration ◽  
Body Wall ◽  
Rna Binding ◽  
Binding Protein ◽  
Neuromuscular Disorders ◽  
Rna Binding Protein ◽  
Nervous System Development ◽  
The Body ◽  
Body Wall Muscle ◽  
Neuroblast Migration

SummaryNeuroblast migration is a critical aspect of nervous system development (e.g., neural crest migration). In an unbiased forward genetic screen, we identified a novel player in neuroblast migration, the ETR-1/CELF1 RNA binding protein. CELF1 RNA binding proteins are involved in multiple aspects of RNA processing including alternative splicing, stability, and translation. We find that a specific mutation in alternatively-spliced exon 8 results in migration defects of the AQR and PQR neurons, and not the embryonic lethality and body wall muscle defects of complete knockdown of the locus. Surprisingly, ETR-1 was required in body wall muscle cells for AQR/PQR migration (i.e. it acts cell non-autonomously). Genetic interactions indicate that ETR-1 acts with Wnt signaling, either in the Wnt pathway or in a parallel pathway. Possibly, ETR-1 is involved in the production of a Wnt signal or a parallel signal by the body wall muscles that controls AQR and PQR neuronal migration. In humans, CELF1 is involved in a number of neuromuscular disorders. If the role of ETR-1/CELF1 is conserved, these disorders might also involve cell or neuronal migration. Finally, we describe a technique of amplicon sequencing to detect rare, cell-specific genome edits by CRISPR/Cas9 in vivo (CRISPR-seq) as an alternative to the T7E1 assay.

scholarly journals The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in Caenorhabditis elegans

2020 ◽  
Vol 10 (7) ◽  
pp. 2365-2376
Author(s):  
Matthew E. Ochs ◽  
Matthew P. Josephson ◽  
Erik A. Lundquist
Keyword(s):  
Neuronal Migration ◽  
Body Wall ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Nervous System Development ◽  
The Body ◽  
Body Wall Muscle ◽  
Link Type ◽  
Neuroblast Migration

Neuroblast migration is a critical aspect of nervous system development (e.g., neural crest migration). In an unbiased forward genetic screen, we identified a novel player in neuroblast migration, the ETR-1/CELF1 RNA binding protein. CELF1 RNA binding proteins are involved in multiple aspects of RNA processing including alternative splicing, stability, and translation. We find that a specific mutation in alternatively-spliced exon 8 results in migration defects of the AQR and PQR neurons, and not the embryonic lethality and body wall muscle defects of complete knockdown of the locus. Surprisingly, ETR-1 was required in body wall muscle cells for AQR/PQR migration (i.e., it acts cell non-autonomously). Genetic interactions indicate that ETR-1 acts with Wnt signaling, either in the Wnt pathway or in a parallel pathway. Possibly, ETR-1 is involved in the production of a Wnt signal or a parallel signal by the body wall muscles that controls AQR and PQR neuronal migration. In humans, CELF1 is involved in a number of neuromuscular disorders. If the role of ETR-1/CELF1 is conserved, these disorders might also involve cell or neuronal migration. Finally, we describe a technique of amplicon sequencing to detect rare, cell-specific genome edits by CRISPR/Cas9 in vivo (CRISPR-seq) as an alternative to the T7E1 assay.

scholarly journals Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

2021 ◽  
Author(s):  
Matthew E. Ochs ◽  
Rebecca McWhirter ◽  
Rob Unckless ◽  
David Miller ◽  
Erik A Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Neuronal Migration ◽  
Body Wall ◽  
Muscle Development ◽  
Stop Codon ◽  
Neuromuscular Disorders ◽  
Muscle Differentiation ◽  
Body Wall Muscle ◽  
Neuroblast Migration ◽  
Alternatively Spliced

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-prime 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.

scholarly journals Caenorhabditis Elegans ETR-1/CELF Has Broad Effects on the Muscle Cell Transcriptome, Including Genes That Regulate Translation and Neuroblast Migration

2021 ◽  
Author(s):  
Matthew Ochs ◽  
Rebecca McWhirter ◽  
Robert Unckless ◽  
David Miller III ◽  
Erik Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Neuronal Migration ◽  
Body Wall ◽  
Muscle Development ◽  
Stop Codon ◽  
Neuromuscular Disorders ◽  
Muscle Differentiation ◽  
Body Wall Muscle ◽  
Neuroblast Migration ◽  
Alternatively Spliced

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.

scholarly journals Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Matthew E. Ochs ◽  
Rebecca M. McWhirter ◽  
Robert L. Unckless ◽  
David M. Miller ◽  
Erik A. Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Neuronal Migration ◽  
Body Wall ◽  
Muscle Development ◽  
Stop Codon ◽  
Neuromuscular Disorders ◽  
Muscle Differentiation ◽  
Body Wall Muscle ◽  
Neuroblast Migration ◽  
Alternatively Spliced

AbstractMigration 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.

scholarly journals The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

2021 ◽  
Author(s):  
Shekoufeh Almasi ◽  
Bernard J. Jasmin
Keyword(s):  
Rna Binding ◽  
Current Knowledge ◽  
Binding Protein ◽  
Neuromuscular Disorders ◽  
Expression Patterns ◽  
Rna Binding Protein ◽  
Rna Metabolism ◽  
Cancer Development ◽  
Cell Functions

AbstractThe double-stranded multifunctional RNA-binding protein (dsRBP) Staufen was initially discovered in insects as a regulator of mRNA localization. Later, its mammalian orthologs have been described in different organisms, including humans. Two human orthologues of Staufen, named Staufen1 (STAU1) and Staufen2 (STAU2), share some structural and functional similarities. However, given their different spatio-temporal expression patterns, each of these orthologues plays distinct roles in cells. In the current review, we focus on the role of STAU1 in cell functions and cancer development. Since its discovery, STAU1 has mostly been studied for its involvement in various aspects of RNA metabolism. Given the pivotal role of RNA metabolism within cells, recent studies have explored the mechanistic impact of STAU1 in a wide variety of cell functions ranging from cell growth to cell death, as well as in various disease states. In particular, there has been increasing attention on the role of STAU1 in neuromuscular disorders, neurodegeneration, and cancer. Here, we provide an overview of the current knowledge on the role of STAU1 in RNA metabolism and cell functions. We also highlight the link between STAU1-mediated control of cellular functions and cancer development, progression, and treatment. Hence, our review emphasizes the potential of STAU1 as a novel biomarker and therapeutic target for cancer diagnosis and treatment, respectively.

235: The RNA-Binding Protein IMP3: A Novel Molecular Marker Predicts Progression of Superficial (TA and T1) Urothelial Carcinomas of Bladder

2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Urothelial Carcinomas
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