Journal Article

Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells

Zhang, Dongmei, Longworth, Michelle S., Vasu, Kommireddy, Ward, Jacqueline R., Deutschman, Emily, Halawani, Dalia, Willard, Belinda, Larson, Peter A., Fox, Paul L., Moran, John V.

2017

Overview

LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine Triphosphatases - genetics / Biology and life sciences / Cancer / Cell Cycle Proteins - genetics / Cellular proteins / Condensin / Cooperation / Deoxyribonucleic acid / DNA / DNA-Binding Proteins - genetics / Epithelial cells / Epithelial Cells - metabolism / Gait / Gene expression / Genetic aspects / Genome, Human / Genomes / Glyceraldehyde / Glyceraldehyde 3-phosphate / Glyceraldehyde-3-phosphate dehydrogenase / Health aspects / Humans / Immunoprecipitation / Inflammation / Initiation complex / Interferon / Interferon-gamma - genetics / Interferon-Stimulated Gene Factor 3 - genetics / Kinases / Long Interspersed Nucleotide Elements - genetics / Medical research / Medicine / Medicine and Health Sciences / Multiprotein Complexes - genetics / Mutation / Myeloid cells / Nuclear Proteins - genetics / Proline-tRNA ligase / Protein Binding / Protein Synthesis Inhibitors / Proteomics / Research and Analysis Methods / Retroelements - genetics / Retrotransposition / Retrotransposons / Ribonucleic acid / RNA / RNA, Messenger - genetics / RNA-protein interactions / Somatic cells / Transcription / Translation / Translation initiation / tRNA / γ-Interferon