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An update on post-transcriptional regulation of retrotransposons

Journal

FEBS LETTERS
Volume 597, Issue 3, Pages 380-406

Publisher

WILEY
DOI: 10.1002/1873-3468.14551

Keywords

autophagy; DNA repair; innate immunity; LINE-1; m(6)A; mobile genome; polyadenylation and uridylation; retrotransposition; retrotransposon; RNA decay

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This article summarizes the current understanding of retrotransposon biology, with a focus on LINE-1. By studying the involvement of post-transcriptional factors, it has been found that retrotransposon expression is tightly regulated to prevent harmful effects. Additionally, this paper discusses the roles of retrotransposons in RNA metabolism, cellular innate immunity, and cellular enzymes.
Retrotransposons, including LINE-1, Alu, SVA, and endogenous retroviruses, are one of the major constituents of human genomic repetitive sequences. Through the process of retrotransposition, some of them occasionally insert into new genomic locations by a copy-paste mechanism involving RNA intermediates. Irrespective of de novo genomic insertions, retrotransposon expression can lead to DNA double-strand breaks and stimulate cellular innate immunity through endogenous patterns. As a result, retrotransposons are tightly regulated by multi-layered regulatory processes to prevent the dangerous effects of their expression. In recent years, significant progress was made in revealing how retrotransposon biology intertwines with general post-transcriptional RNA metabolism. Here, I summarize current knowledge on the involvement of post-transcriptional factors in the biology of retrotransposons, focusing on LINE-1. I emphasize general RNA metabolisms such as methylation of adenine (m(6)A), RNA 3 '-end polyadenylation and uridylation, RNA decay and translation regulation. I discuss the effects of retrotransposon RNP sequestration in cytoplasmic bodies and autophagy. Finally, I summarize how innate immunity restricts retrotransposons and how retrotransposons make use of cellular enzymes, including the DNA repair machinery, to complete their replication cycles.

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