RRC ID 59490
著者 Fischer SEJ, Ruvkun G.
タイトル Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons.
ジャーナル Proc Natl Acad Sci U S A
Abstract Endogenous retroviruses and long terminal repeat (LTR) retrotransposons are mobile genetic elements that are closely related to retroviruses. Desilenced endogenous retroviruses are associated with human autoimmune disorders and neurodegenerative diseases. Caenorhabditis elegans and related Caenorhabditis spp. contain LTR retrotransposons and, as described here, numerous integrated viral genes including viral envelope genes that are part of LTR retrotransposons. We found that both LTR retrotransposons and endogenous viral elements are silenced by ADARs [adenosine deaminases acting on double-stranded RNA (dsRNA)] together with the endogenous RNA interference (RNAi) factor ERI-6/7, a homolog of MOV10 helicase, a retrotransposon and retrovirus restriction factor in human. siRNAs corresponding to integrated viral genes and LTR retrotransposons, but not to DNA transposons, are dependent on the ADARs and ERI-6/7. siRNAs corresponding to palindromic repeats are independent of the ADARs and ERI-6/7, and are in fact increased in adar- and eri-6/7-defective mutants because of an antiviral RNAi response to dsRNA. Silencing of LTR retrotransposons is dependent on downstream RNAi factors and P granule components but is independent of the viral sensor DRH-1/RIG-I and the nuclear Argonaute NRDE-3. The activation of retrotransposons in the ADAR- and ERI-6/7/MOV10-defective mutant is associated with the induction of the unfolded protein response (UPR), a common response to viral infection. The overlap between genes induced upon viral infection and infection with intracellular pathogens and genes coexpressed with retrotransposons suggests that there is a common response to different types of foreign elements that includes a response to proteotoxicity presumably caused by the burden of replicating pathogens and expressed retrotransposons.
巻・号 117(11)
ページ 5987-5996
公開日 2020-3-17
DOI 10.1073/pnas.1919028117
PII 1919028117
PMID 32123111
PMC PMC7084138
MeSH Adenosine Deaminase / genetics Adenosine Deaminase / metabolism Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / virology Caenorhabditis elegans Proteins / metabolism DNA Helicases / metabolism DNA, Viral / metabolism Endogenous Retroviruses / genetics* Endoplasmic Reticulum Stress / genetics Gene Expression Regulation, Viral Genes, Viral / genetics Host Microbial Interactions / genetics* Humans RNA Interference* RNA, Double-Stranded / metabolism RNA, Viral / metabolism Retroelements / genetics* Sequence Homology, Amino Acid Terminal Repeat Sequences / genetics Unfolded Protein Response / genetics
IF 9.58
引用数 0
リソース情報
線虫 tm668