Endogenous Double-Stranded RNA

Sadeq, Shaymaa; Al-Hashimi, Surar; Cusack, Carmen M.; Werner, Andreas

doi:10.3390/ncrna7010015

Cited by 46 publications

(41 citation statements)

References 155 publications

(135 reference statements)

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“…The data that p150 is key to negatively regulating interferon responses and that loss of function variants the Zα domain are associated with type I interferonopathies provide strong evidence for this mechanism. The model incorporates many elements of previous proposals on how MDA5 discriminates nonself from self that are based on the localization, structure, and availability of dsRNA [54][55][56][57][58]. None of these earlier models completely fit with the data.…”

Section: Alternative Models Of Self-recognition By Mda5mentioning

confidence: 99%

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

Herbert

2021

PLoS Genet

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Double-stranded RNA (dsRNA) is produced both by virus and host. Its recognition by the melanoma differentiation–associated gene 5 (MDA5) initiates type I interferon responses. How can a host distinguish self-transcripts from nonself to ensure that responses are targeted correctly? Here, I discuss a role for MDA5 helicase in inducing Z-RNA formation by Alu inverted repeat (AIR) elements. These retroelements have highly conserved sequences that favor Z-formation, creating a site for the dsRNA-specific deaminase enzyme ADAR1 to dock. The subsequent editing destabilizes the dsRNA, ending further interaction with MDA5 and terminating innate immune responses directed against self. By enabling self-recognition, Alu retrotransposons, once invaders, now are genetic elements that keep immune responses in check. I also discuss the possible but less characterized roles of the other helicases in modulating innate immune responses, focusing on DExH-box helicase 9 (DHX9) and Mov10 RISC complex RNA helicase (MOV10). DHX9 and MOV10 function differently from MDA5, but still use nucleic acid structure, rather than nucleotide sequence, to define self. Those genetic elements encoding the alternative conformations involved, referred to as flipons, enable helicases to dynamically shape a cell’s repertoire of responses. In the case of MDA5, Alu flipons switch off the dsRNA-dependent responses against self. I suggest a number of genetic systems in which to study interactions between flipons and helicases further.

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Section: Alternative Models Of Self-recognition By Mda5mentioning

confidence: 99%

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

Herbert

2021

PLoS Genet

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“…This observation contrasts with the accumulation of repetitive elements on the X Chromosome (Komissarov et al 2011). The significant contribution of Alu and LINE-1 elements to dsRNA formation in somatic cells (Sadeq et al 2021) may again point to different biological roles of dsRNA formation in germ and somatic cells.…”

Section: Discussionmentioning

confidence: 93%

Widespread formation of double-stranded RNAs in testis

et al. 2021

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The testis transcriptome is highly complex and includes RNAs that potentially hybridize to form double-stranded RNA (dsRNA). We isolated dsRNA using the monoclonal J2 antibody and deep-sequenced the enriched samples from testes of juvenile Dicer1 knockout mice, age-matched controls, and adult animals. Comparison of our data set with recently published data from mouse liver revealed that the dsRNA transcriptome in testis is markedly different from liver: In testis, dsRNA-forming transcripts derive from mRNAs including promoters and immediate downstream regions, whereas in somatic cells they originate more often from introns and intergenic transcription. The genes that generate dsRNA are significantly expressed in isolated male germ cells with particular enrichment in pachytene spermatocytes. dsRNA formation is lower on the sex (X and Y) chromosomes. The dsRNA transcriptome is significantly less complex in juvenile mice as compared to adult controls and, possibly as a consequence, the knockout of Dicer1 has only a minor effect on the total number of transcript peaks associated with dsRNA. The comparison between dsRNA-associated genes in testis and liver with a reported set of genes that produce endogenous siRNAs reveals a significant overlap in testis but not in liver. Testis dsRNAs also significantly associate with natural antisense genes—again, this feature is not observed in liver. These findings point to a testis-specific mechanism involving natural antisense transcripts and the formation of dsRNAs that feed into the RNA interference pathway, possibly to mitigate the mutagenic impacts of recombination and transposon mobilization.

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“…Some regions are the main targets of TEs, probably because of their accessibility [ 88 , 89 , 90 ]. In addition, patchy distribution due to the accessibility effect could be reinforced by the existence of low recombination rates, leading us to consider some of these regions as TE graveyards [ 91 , 92 , 93 , 94 ].…”

Section: Long Term Co-evolution Of Transposable Elements and Genomes: Domestication And Exaptationmentioning

confidence: 99%

Taming, Domestication and Exaptation: Trajectories of Transposable Elements in Genomes

Capy

2021

Cells

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During evolution, several types of sequences pass through genomes. Along with mutations and internal genetic tinkering, they are a useful source of genetic variability for adaptation and evolution. Most of these sequences are acquired by horizontal transfers (HT), but some of them may come from the genomes themselves. If they are not lost or eliminated quickly, they can be tamed, domesticated, or even exapted. Each of these processes results from a series of events, depending on the interactions between these sequences and the host genomes, but also on environmental constraints, through their impact on individuals or population fitness. After a brief reminder of the characteristics of each of these states (taming, domestication, exaptation), the evolutionary trajectories of these new or acquired sequences will be presented and discussed, emphasizing that they are not totally independent insofar as the first can constitute a step towards the second, and the second is another step towards the third.

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Endogenous Double-Stranded RNA

Cited by 46 publications

References 155 publications

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

Widespread formation of double-stranded RNAs in testis

Taming, Domestication and Exaptation: Trajectories of Transposable Elements in Genomes

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