Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in <i>Caenorhabditis elegans</i> Somatic Tissues

Blazie, Stephen M; Geissel, Heather C; Wilky, Henry; Joshi, Rajan; Newbern, Jason M.; Mangone, Marco

doi:10.1534/genetics.116.196774

Cited by 74 publications

(142 citation statements)

References 91 publications

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“…There is evidence that shows increased expression of Tox3 leads to neural protection and facilitates recovery in spinal cord injury in mice via protection of oligodendrocytes (Bastien et al, 2015). The closest predicted ortholog of TOX3 in C. elegans is HMG-6, which has been shown to be expressed in neurons and sperm (Blazie et al, 2017; Lockhead et al, 2016; Spencer et al, 2011). However, there has not been any evidence establishing its function in the nematode so far.…”

Section: Elegans Homologs Of Rls and Their Functionmentioning

confidence: 99%

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

Chen

Ijomone

Lee

et al. 2019

Pharmacology of Restless Legs Syndrome (RLS)

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Restless legs syndrome (RLS) is a common neurological disorder in the US. This disorder is characterized by an irresistible urge to move the legs, although the symptoms vary in a wide range. The pathobiology of RLS has been linked to iron (Fe) deficiency and dopaminergic (DAergic) dysfunction. Several genetic factors have been reported to increase the risk of RLS. Caenorhabditis elegans (C. elegans) is a well-established animal model with a fully sequenced genome, which is highly conserved with mammals. Given the detailed knowledge of its genomic architecture, ease of genetic manipulation and conserved biosynthetic and metabolic pathways, as well as its small size, ease of maintenance, speedy generation time and large brood size, C. elegans provides numerous advantages in studying RLS-associated gene-environment interactions. Here we will review current knowledge about RLS symptoms, pathology and treatments, and discuss the application of C. elegans in RLS study, including the worm homologous genes and methods that could be performed to advance the pathophysiology RLS.

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Section: Elegans Homologs Of Rls and Their Functionmentioning

confidence: 99%

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

Chen

Ijomone

Lee

et al. 2019

Pharmacology of Restless Legs Syndrome (RLS)

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“…While the use of whole worms allows for the quantification systemic changes on translational regulation or effects occurring in large tissues like the intestine, tissue specific effects, like RNA editing in the neurons, are likely lost by averaging the effect over all other tissues. The use of tagged RNA binding proteins, like poly A binding protein, expressed by tissue specific promoters has been used in C. elegans to quantify tissue-specific gene expression in total mRNA pools (Blazie et al, 2015(Blazie et al, , 2017. Future studies may rely on similar technology to identify genome-wide tissue-specific patterns of differential processing and expression.…”

Section: Dr Increases As Products and Differentially Regulates Nmd Tamentioning

confidence: 99%

Dietary restriction induces post-transcriptional regulation of longevity genes

Rollins

Snow

Kapahi

et al. 2019

Preprint

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Dietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3' UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5' UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

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“…Calculating poly(A) tail lengths requires a sequencing approach capable of resolving long homopolymers, and determining 3'UTR structures requires an experimental or computational means of determining which reads reflect the 3' most base included in the transcript before cleavage and polyadenylation. The specialized protocols and analyses used to measure poly(A) tail length and identify 3'UTRs with short read sequencing approaches cannot directly link these measurements to their splice isoform of origin, and in the case of 3'UTR identification instead rely on assigning putative cleavage sites to the nearest overlapping or upstream gene (Subtelny et al 2014;Chang et al 2014;Mangone et al 2010;Jan et al 2011;Blazie et al 2017;Diag et al 2018) .…”

Section: Introductionmentioning

confidence: 99%

The full-length transcriptome ofC. elegansusing direct RNA sequencing

Roach

Sadowski

Alessi

et al. 2019

Preprint

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Current transcriptome annotations have largely relied on short read lengths intrinsic to most widely used high-throughput cDNA sequencing technologies. For example, in the annotation of the Caenorhabditis elegans transcriptome, more than half of the transcript isoforms lack full-length support and instead rely on inference from short reads that do not span the full length of the isoform. We applied nanopore-based direct RNA sequencing to characterize the developmental polyadenylated transcriptome of C. elegans . Taking advantage of long reads spanning the full length of mRNA transcripts, we provide support for 20,902 splice isoforms across 14,115 genes, without the need for computational reconstruction of gene models. Of the isoforms identified, 2,188 are novel splice isoforms not present in the Wormbase WS265 annotation. Furthermore, we identified 16,325 3' untranslated region (3'UTR) isoforms, 2,304 of which are novel and do not fall within 10 bp of existing 3'UTR datasets and annotations. Combining 3'UTRs and splice isoforms we identified 25,944 full-length isoforms. We also determined that poly(A) tail lengths of transcripts vary across development, as do the strengths of previously reported correlations between poly(A) tail length and expression level, and poly(A) tail length and 3'UTR length. Finally, we have formatted this data as a publically accessible track hub, enabling researchers to explore this dataset easily in a genome browser.

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Alternative Polyadenylation Directs Tissue-Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues

Abstract: Alternative polyadenylation (APA) is observed in virtually all metazoans and results in mRNA isoforms with different 3’ends. It is routinely...

Cited by 74 publications

References 91 publications

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

Dietary restriction induces post-transcriptional regulation of longevity genes

The full-length transcriptome ofC. elegansusing direct RNA sequencing

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