LINE-1: an emerging initiator of cGAS-STING signalling and inflammation that is dysregulated in disease

Biochem Cell Biol. 2023 Aug 29. doi: 10.1139/bcb-2023-0134. Online ahead of print.ABSTRACTThe cGAS-STING axis integrates DNA damage and cellular stress with type I interferon (IFN) signalling to facilitate transcriptional changes underlying inflammatory stress responses. The cGAS-STING pathway responds to cytosolic DNA in the form of dsDNA, micronuclei, and LINE-1 (L1) retroelements. L1 retroelements are a class of self-propagating non-LTR transposons that have remained highly active in our genomes. L1 retroelements are emerging as important inducers of cGAS-STING and interferon signalling, which are often dysregulated in several diseases including cancer. A key repressor of cGAS-STING and L1 activity is the exonuclease TREX1, and loss of TREX1 promotes the accumulation of L1. In addition, L1 dysregulation is becoming a common theme among diseases with chronic induction of type I IFN signalling through cGAS-STING such as Aicardi-Goutières syndrome, Fanconi anemia, and Dermatomyotisis. Although TREX1 is highly conserved in tetrapod species, other suppressor proteins exist that inhibit L1 retrotransposition. These suppressor genes when mutated are often associated with diseases characterized by unchecked inflammation that is associated with high cGAS-STING activity and elevated levels of L1 expression. In this review, we discuss these interconnected pathways of L1 suppression, and their role in the regulation of cGAS-STING and inflammation in disease.PMID:37643478 | DOI:10.113...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Source Type: research