Interplay between RNA interference and transposable elements in mammals

Cornec, Alexis; Poirier, Enzo Z.

doi:10.3389/fimmu.2023.1212086

Cited by 8 publications

(5 citation statements)

References 82 publications

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“…TEs constitute around 45% of the human genome and are divided into two families, the DNA transposons and the retrotransposons (11)(12)(13)(14)(15). A subset of elements belonging to the latter class still remain active in the human genome (16), this includes the long interspersed nuclear elements (LINEs), Alu, and SINE-VNTR-Alu (SVA) elements, which have demonstrated not only to be drivers of genetic diversity by contributing to genome variation, gene regulation and hominid evolution (17-19) but also to be involved in disease development and progression (16,(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus

Fröhlich,

Hughes,

Middlehurst

et al. 2023

Front. Neurol.

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BackgroundSINE-VNTR-Alu (SVA) retrotransposons are hominid-specific elements which have been shown to play important roles in processes such as chromatin structure remodelling and regulation of gene expression demonstrating that these repetitive elements exert regulatory functions. We have previously shown that the presence or absence of a specific SVA element, termed SVA_67, was associated with differential expression of several genes at the MAPT locus, a locus associated with Parkinson’s Disease (PD) and frontotemporal dementia. However, we were not able to demonstrate that causation of differential gene expression was directed by the SVA due to lack of functional validation.MethodsWe performed CRISPR to delete SVA_67 in the HEK293 cell line. Quantification of target gene expression was performed using qPCR to assess the effects on expression in response to the deletion of SVA_67. Differences between CRISPR edit and control cell lines were analysed using two-tailed t-test with a minimum 95% confidence interval to determine statistical significance.ResultsIn this study, we provide data highlighting the SVA-specific effect on differential gene expression. We demonstrate that the hemizygous deletion of the endogenous SVA_67 in CRISPR edited cell lines was associated with differential expression of several genes at the MAPT locus associated with neurodegenerative diseases including KANSL1, MAPT and LRRC37A.DiscussionThis data is consistent with our previous bioinformatic work of differential gene expression analysis using transcriptomic data from the Parkinson’s Progression Markers Initiative (PPMI) cohort. As SVAs have regulatory influences on gene expression, and insertion polymorphisms contribute to interpersonal differences in expression patterns, these results highlight the potential contribution of these elements to complex diseases with potentially many genetic components, such as PD.

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Section: Introductionmentioning

confidence: 99%

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus

Fröhlich,

Hughes,

Middlehurst

et al. 2023

Front. Neurol.

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“…RNAi-based pathways are used by eukaryotic organisms for several regulatory mechanisms, such as control of genes and genome integrity, defense against viruses, and control of developmental factors. RNAi seems to be involved in the control of transposable elements (TEs) in plants and animals [ 226 , 237 , 238 , 239 ]. Mutations in RNAi pathway genes can lead to a loss of silencing effect along with increased activity of TEs [ 226 , 237 , 239 , 240 ].…”

Section: Rna Interference (Rnai): First Evidence and An Overview Of M...mentioning

confidence: 99%

“…RNAi seems to be involved in the control of transposable elements (TEs) in plants and animals [ 226 , 237 , 238 , 239 ]. Mutations in RNAi pathway genes can lead to a loss of silencing effect along with increased activity of TEs [ 226 , 237 , 239 , 240 ]. In plants, RNAi is closely linked to viral defense; in fact, mutants of the gene related to the PTGS pathway have shown increased susceptibility to viruses, and, on the other hand, many plant viruses have developed genes to hinder the RNAi response in wounded cells [ 209 , 241 , 242 , 243 , 244 , 245 , 246 , 247 ].…”

Section: Rna Interference (Rnai): First Evidence and An Overview Of M...mentioning

confidence: 99%

Challenges and Opportunities Arising from Host–Botrytis cinerea Interactions to Outline Novel and Sustainable Control Strategies: The Key Role of RNA Interference

Spada,

Pugliesi,

Fambrini

et al. 2024

IJMS

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The necrotrophic plant pathogenic fungus Botrytis cinerea (Pers., 1794), the causative agent of gray mold disease, causes significant losses in agricultural production. Control of this fungal pathogen is quite difficult due to its wide host range and environmental persistence. Currently, the management of the disease is still mainly based on chemicals, which can have harmful effects not only on the environment and on human health but also because they favor the development of strains resistant to fungicides. The flexibility and plasticity of B. cinerea in challenging plant defense mechanisms and its ability to evolve strategies to escape chemicals require the development of new control strategies for successful disease management. In this review, some aspects of the host-pathogen interactions from which novel and sustainable control strategies could be developed (e.g., signaling pathways, molecules involved in plant immune mechanisms, hormones, post-transcriptional gene silencing) were analyzed. New biotechnological tools based on the use of RNA interference (RNAi) are emerging in the crop protection scenario as versatile, sustainable, effective, and environmentally friendly alternatives to the use of chemicals. RNAi-based fungicides are expected to be approved soon, although they will face several challenges before reaching the market.

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“…Before the discovery of RNA interference, many genes with RNAi functions were initially identified and characterized for their roles in promoting genome integrity via the suppression of transposon activity. Currently, we understand that RNAi pathways function to distinguish “self” versus “non-self” transcripts to protect the cells against foreign nucleic acids [ 65 , 232 , 233 , 234 ]. Naturally, these functions could be extended to external pathogens, such as viruses and bacteria.…”

Section: Examples Of Epigenetic Inheritance Induced By Biotic and Abi...mentioning

confidence: 99%

Inheritance of Stress Responses via Small Non-Coding RNAs in Invertebrates and Mammals

Ow,

Hall

2023

Epigenomes

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While reports on the generational inheritance of a parental response to stress have been widely reported in animals, the molecular mechanisms behind this phenomenon have only recently emerged. The booming interest in epigenetic inheritance has been facilitated in part by the discovery that small non-coding RNAs are one of its principal conduits. Discovered 30 years ago in the Caenorhabditis elegans nematode, these small molecules have since cemented their critical roles in regulating virtually all aspects of eukaryotic development. Here, we provide an overview on the current understanding of epigenetic inheritance in animals, including mice and C. elegans, as it pertains to stresses such as temperature, nutritional, and pathogenic encounters. We focus on C. elegans to address the mechanistic complexity of how small RNAs target their cohort mRNAs to effect gene expression and how they govern the propagation or termination of generational perdurance in epigenetic inheritance. Presently, while a great amount has been learned regarding the heritability of gene expression states, many more questions remain unanswered and warrant further investigation.

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Interplay between RNA interference and transposable elements in mammals

Cited by 8 publications

References 82 publications

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus

Challenges and Opportunities Arising from Host–Botrytis cinerea Interactions to Outline Novel and Sustainable Control Strategies: The Key Role of RNA Interference

Inheritance of Stress Responses via Small Non-Coding RNAs in Invertebrates and Mammals

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