An LTR Retrotransposon-derived LncRNA Interacts with RNF169 to Promote Homologous Recombination

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2019 Sep 6

PMID 31486214

Citations 21

Authors

Bing Deng

Wenli Xu

Zelin Wang

Chang Liu

Penghui Lin

Bin Li

Qiaojuan Huang

Jianhua Yang

Hui Zhou

Lianghu Qu

Affiliations

Soon will be listed here.

Abstract

LTR retrotransposons are abundant repetitive elements in the human genome, but their functions remain poorly understood. Here, we report the function and regulatory mechanism of an ERV-9 LTR retrotransposon-derived lncRNA called p53-regulated lncRNA for homologous recombination (HR) repair 1 (PRLH1) in human cells. PRLH1 is highly expressed in p53-mutated hepatocellular carcinoma (HCC) samples and promotes cell proliferation in p53-mutated HCC cells, and its transcription is promoted by NF-Y and suppressed by p53. Mechanistically, PRLH1 specifically binds to an uncharacterized domain of RNF169 through two GCUUCA boxes in its 5' terminal region to form a DNA repair complex that supplants 53BP1 at double-strand break (DSB) sites and then promotes the initiation of HR repair. Notably, PRLH1 is essential for the stabilization of RNF169, acting as an RNA platform to recruit and assemble HR protein factors. This study characterizes PRLH1 as a novel HR-promoting factor and provides new insights into the function and mechanism of LTR retrotransposon-derived lncRNAs.

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