Phase separation of the LINE-1 ORF1 protein is mediated by the N-terminus and coiled-coil domain.

ABSTRACT: Long interspersed nuclear element-1 (L1) is a retrotransposable element that autonomously replicates in the human genome, resulting in DNA damage and genomic instability. Activation of L1 in senescent cells triggers a type I interferon response and age-associated inflammation. Two open reading frames encode an ORF1 protein functioning as messenger RNA chaperone and an ORF2 protein providing catalytic activities necessary for retrotransposition. No function has been identified for the conserved, disordered N-terminal region of ORF1. Using microscopy and NMR spectroscopy, we demonstrate that ORF1 forms liquid droplets in vitro in a salt-dependent manner and that interactions between its N-terminal region and coiled-coil domain are necessary for phase separation. Mutations disrupting blocks o

SUBMITTER: Newton JC 

PROVIDER: S-EPMC8390800 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature