Endogenous siRNAs: regulators of internal affairs

Piatek, Monica J.; Werner, Andreas

doi:10.1042/bst20140068

Cited by 70 publications

(45 citation statements)

References 56 publications

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“…Particularly, three genes in the ERGO-1 siRNA pathway (ergo-1, eri-6/eri-7, and eri-9; (Piatek and Werner 2014)) are not present in this species (Kanzaki, et al 2018). As ergo-1 encodes an RNA-silencing argonaut protein (Yigit, et al 2006), and as small RNA's are known to regulate transposable elements in other systems (Piatek and Werner 2014), the loss of these genes in C. inopinata poses a tantalizing line of future research for understanding its repetitive landscape. Furthermore, the demographic and evolutionary history of a lineage can drive variation in the distributions of transposable elements (Lockton, et al 2008), and this remains unexplored in C. inopinata.…”

Section: (Continuing From Previous Page)mentioning

confidence: 98%

Degradation of the repetitive genomic landscape in a close relative ofC. elegans

Woodruff

Teterina

2019

Preprint

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AbstractThe abundance, diversity, and genomic distribution of repetitive elements is highly variable among species. These patterns are thought to be driven in part by reproductive mode and the interaction of selection and recombination, and recombination rates typically vary by chromosomal position. In the nematode C. elegans, repetitive elements are enriched at chromosome arms and depleted on centers, and this mirrors the chromosomal distributions of other genomic features such as recombination rate. How conserved is this genomic landscape of repeats, and what evolutionary forces maintain it? To address this, we compared the genomic organization of repetitive elements across five Caenorhabditis species with chromosome-level assemblies. As previously reported, repeat content is enriched on chromosome arms in most Caenorhabditis species, and no obvious patterns of repeat content associated with reproductive mode were observed. However, the fig-associated Caenorhabditis inopinata has experienced rampant repetitive element expansion and reveals no association of global repeat content with chromosome position. Patterns of transposable element superfamily-specific distributions reveal this global pattern is driven largely by a few transposable element superfamilies that in C. inopinata have expanded in number and have weak associations with chromosome position. Additionally, 15% of predicted protein-coding genes in C. inopinata align to transposon-related proteins. When these are excluded, C. inopinata has no enrichment of genes in chromosome centers, in contrast to its close relatives who all have such clusters. Forward evolutionary simulations reveal that chromosomal heterogeneity in recombination rate is insufficient for generating structured genomic repetitive landscapes. Instead, heterogeneity in the fitness effects of transposable element insertion is needed to promote heterogeneity in repetitive landscapes. Thus, patterns of gene density along chromosomes are likely drivers of global repetitive landscapes in this group, although other historical or genomic factors are needed to explain the idiosyncrasy of genomic organization of various transposable element taxa within C. inopinata. Taken together, these results highlight the power of comparative genomics and evolutionary simulations in testing hypotheses regarding the causes of genome organization.

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Section: (Continuing From Previous Page)mentioning

confidence: 98%

Degradation of the repetitive genomic landscape in a close relative ofC. elegans

Woodruff

Teterina

2019

Preprint

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“…In particular, such ncRNAs were shown to decrease the expression from homologous DNA sequences in trans , possibly acting through the canonical pathways of endogenous siRNAs (endo‐siRNAs). Thus, these endo‐siRNA‐like molecules may promote post‐transcriptional silencing of complementary mRNAs in the cytoplasm or regulate gene transcription of the damaged locus by cotranscriptional mechanisms, including those involving chromatin modifications (Fig. ).…”

Section: Transcription At Dsbsmentioning

confidence: 99%

Express or repress? The transcriptional dilemma of damaged chromatin

et al. 2017

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The fine modulation of transcriptional activity around DNA lesions is essential to carefully regulate the crosstalk between the activation of the DNA damage response, DNA repair and transcription, particularly when the lesion occurs next to actively transcribed genes. Recently, several studies have been carried out to investigate how DNA lesions impact on local transcription, but the emerging model remains incomplete. Transcription of genes around damaged DNA is actively downregulated by the DNA damage response through different mechanisms, which appear specific to the chromatin context, the type of DNA damage or its complexity. Intriguingly, emerging evidence also indicates that transcription of noncoding RNAs (ncRNAs) is induced at sites of DNA damage, producing small ncRNAs that are, in turn, required for a full DNA damage response activation. We discuss here these recent findings, highlighting the major unresolved questions in the field, and propose ways to reconcile these apparently contradictory observations.

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“…Alternatively, siRNA can also be endogenously derived from the dicer cleavage of double-stranded RNA in the cytoplasm. 13,14 The incorporation of siRNA with RISC and the subsequent mRNA degradation mechanism are similar to those for miRNA. 15 The siRNA sequence can be artificially designed to exquisitely regulate single gene expression because siRNA is completely complementary to the targeted mRNA sequence.…”

Section: Introductionmentioning

confidence: 84%

RNA interference-based nanosystems for inflammatory bowel disease therapy

Guo¹,

Jiang²,

Gui³

2016

IJN

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Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is a chronic, recrudescent disease that invades the gastrointestinal tract, and it requires surgery or lifelong medicinal therapy. The conventional medicinal therapies for IBD, such as anti-inflammatories, glucocorticoids, and immunosuppressants, are limited because of their systemic adverse effects and toxicity during long-term treatment. RNA interference (RNAi) precisely regulates susceptibility genes to decrease the expression of proinflammatory cytokines related to IBD, which effectively alleviates IBD progression and promotes intestinal mucosa recovery. RNAi molecules generally include short interfering RNA (siRNA) and microRNA (miRNA). However, naked RNA tends to degrade in vivo as a consequence of endogenous ribonucleases and pH variations. Furthermore, RNAi treatment may cause unintended off-target effects and immunostimulation. Therefore, nanovectors of siRNA and miRNA were introduced to circumvent these obstacles. Herein, we introduce non-viral nanosystems of RNAi molecules and discuss these systems in detail. Additionally, the delivery barriers and challenges associated with RNAi molecules will be discussed from the perspectives of developing efficient delivery systems and potential clinical use.

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Endogenous siRNAs: regulators of internal affairs

Cited by 70 publications

References 56 publications

Degradation of the repetitive genomic landscape in a close relative ofC. elegans

Degradation of the repetitive genomic landscape in a close relative ofC. elegans

Express or repress? The transcriptional dilemma of damaged chromatin

RNA interference-based nanosystems for inflammatory bowel disease therapy

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