Recognize Yourself—Innate Sensing of Non-LTR Retrotransposons

Lagisquet, Justine; Zuber, K; Gramberg, Thomas

doi:10.3390/v13010094

Cited by 8 publications

(7 citation statements)

References 127 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that cytoplasmic LINE-1 RNA and cDNA can trigger the IFN-I response (Lagisquet et al, 2021 ). We therefore speculated that ZCCHC3 may repress LINE-1 elements replication and retrotransposition, which might directly diminish the accumulation of RNA or cDNA derived from LINE-1 elements, thus diminishing LINE-1-triggered innate response.…”

Section: Resultsmentioning

confidence: 99%

The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

Zhang

Guo

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Long-interspersed element 1 (LINE-1) is an autonomous non-LTR retrotransposon. Its replication can cause mutation and rearrangement of host genomic DNA, which may result in serious genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we reported that CCHC-type zinc-finger protein ZCCHC3 can repress LINE-1 retrotransposition, and this activity is closely related to its zinc-finger domain. Further studies show that ZCCHC3 can post-transcriptionally diminish the LINE-1 RNA level. The association of ZCCHC3 with both LINE-1 RNA and ORF1 suggests that ZCCHC3 interacts with LINE-1 RNP and consequently causes its RNA degradation. These data demonstrate collectively that ZCCHC3 contributes to the cellular control of LINE-1 replication.

show abstract

Section: Resultsmentioning

confidence: 99%

The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

Zhang

Guo

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…For example, in humans, SINE Alu elements have been found to be involved in the inflammatory pathway: upon viral infection, the interferon 1 mediates the overexpression of Alus which functions as an amplifier of the immune response by stimulating intracellular viral RNA sensor systems [57,58]. Despite, the positive involvement of SINEs in the human immune response, the same upregulation of Alus, or the excessive sensitivity of the viral RNA sensors, has been linked to autoimmune diseases [59][60][61]. Furthermore, as non-coding RNAs are emerging as essential component of neuroinflammation, some studies have included Alu SINEs as possible promoters of neurodegenerative diseases [62].…”

Section: Discussionmentioning

confidence: 99%

Involvement of non-LTR retrotransposons in mammal cancer incidence and ageing

Ricci

Peona

Taccioli

2021

Preprint

View full text Add to dashboard Cite

The natural occurrence of closely related species that show drastic differences in lifespan and cancer incidence raised the interest in finding the particular adaptations and genomic characteristics underlying the evolution of long lifespans. Studies on transposable elements (TEs) have more and more linked them to ageing and cancer development. In this study, we compared the TE content and dynamics in the genomes of four Rodent and six Chiroptera species that show very different lifespans and cancer susceptibility including the long-lived and refractory to cancer naked mole rat (Heterocephalus glaber), the long-lived fruit bats (Pteropus vampyrus, Rousettus aegypticaus) and the short-lived velvety free-tailed bat (Molossus molossus). By analysing the patterns of recent TE accumulation (TEs that are potentially currently active) in high-quality genome assemblies, we found that the shared genomic characteristics between long-lived species that are refractory to cancer, is the strong suppression, or negative selection against the accumulation, of non-LTR retrotransposons. All the short-lived species did show a recent accumulation of these TEs. Non-LTR retrotransposons have been often found to take part in the immune response of the host against viral infections, but their dysregulation can lead to phenomena of "sterile inflammation" and "inflammageing". Therefore, we hypothesise that the uncontrolled non-LTR retrotransposon activity is an important factor explaining the evolution of shorter lifespans in both Rodents and Chiroptera species and potentially in all mammals. Finally, these results suggest that non-LTR retrotransposons can be agents promoting cancer and ageing in mammals thus they may be targets of future oncological therapies.

show abstract

“…Retroelements are classified as long terminal repeat (LTR) such as human endogenous retroviruses (HERVs) and non-LTR such as long interspersed elements (LINEs) and short interspersed elements (SINEs) according to their structures (Figure 1). Additionally, retroelements possessing reverse transcriptase for their transposition are categorized as autonomous such as HERVs and LINEs whereas non-autonomous ones such as SINEs and Alu elements (highly repetitive short repeat sequences digested by Alu endonuclease from Arthrobacter luteus) use LINE-1 (L1) machinery for their relocation [1][2][3]. Reverse transcription of LTR retroviral RNA includes binding of a cellular transfer RNA (tRNA) to the primer binding site in the viral RNA genome.…”

Section: Introductionmentioning

confidence: 99%

Involvement of retroelements in the autoimmune response in humans

Okay

2022

Exploration of Medicine

View full text Add to dashboard Cite

Retroelements are mobile genomic components requiring an RNA intermediate which is reverse-transcribed into complementary DNA for transposition. Human genome contains a vast amount of retroelements including retrotransposons and endogenous retroviruses. These elements are categorized according to presence or absence of long terminal repeats, LTRs or non-LTRs, as well as autonomous and non-autonomous according to involvement of reverse transcriptase. The retroelements have been accumulated in mammalian genomes over all evolutionary times through vertical transmission, and many of them were inactivated through accumulation of mutations. However, the retroelements entered into genome within the last 200,000 years are mostly functional. Some of the active retroelements are associated with varying autoimmune diseases because anti-retroelement antibodies might cross-react with other proteins in the human body. For instance, autoimmunity and inflammation could be stimulated by increased expression of long interspersed element 1 (LINE-1 or L1) or decreased L1 degradation. Different regulation of L1 expression might be related to the genetic and sex-related variations or environmental factors. Activation of retroelements is also controlled by epigenetic silencing mechanisms such as histone modification. Elevated levels of L1 retroelements could trigger the production of type I interferon, a crucial innate defense mechanism in mammals against viruses, and systemic autoimmune response is induced. Loss-of-function in some deoxyribonucleases (DNases) such as three prime repair exonuclease 1 that degrades reverse-transcribed DNA is also related to autoimmune diseases. Additionally, human endogenous retroviruses also play a role in autoimmune diseases. Involvement of retroelements in autoimmune disorders is exemplified with three diseases, i.e. systemic lupus erythematosus, Aicardi–Goutières syndrome, and multiple sclerosis.

show abstract

Recognize Yourself—Innate Sensing of Non-LTR Retrotransposons

Cited by 8 publications

References 127 publications

The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

Involvement of non-LTR retrotransposons in mammal cancer incidence and ageing

Involvement of retroelements in the autoimmune response in humans

Contact Info

Product

Resources

About