Abstract
Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic “parasites”, focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research.
Highlights
Sixty-five years on from Barbara McClintock’s seminal discovery of mobile DNA [1] we understand that genomes are dynamic and changeable, with transposable elements (TEs) being major contributors to their fluidity
While Long Interspersed Elements (LINEs)-1 proteins and RNA concentrate in stress granules (SGs) and processing bodies (PBs) along with factors linked with their restriction, a direct role for cytoplasmic granules in modulating retrotransposition remains unclear
Zhang et al [254] hypothesized that RNASEL is activated by double-stranded regions existing within L1 RNA or that are formed by annealing of complementary transcripts generated by the sense and antisense promoters of the L1 5' untranslated region (UTR), Three prime repair exonuclease 1 (TREX1) TREX1, the most abundant 3′–5′ DNA exonuclease in mammalian cells, targets reverse-transcribed retroviral cDNAs to prevent their accumulation in the cytosol
Summary
Sixty-five years on from Barbara McClintock’s seminal discovery of mobile DNA [1] we understand that genomes are dynamic and changeable, with transposable elements (TEs) being major contributors to their fluidity. While LINE-1 proteins and RNA concentrate in SGs and PBs along with factors linked with their restriction, a direct role for cytoplasmic granules in modulating retrotransposition remains unclear.
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