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

• DOI: 10.1371/journal.pgen.1007051
• Publication Date: 2017-10-13T17:23:04Z
• Authors: Jacqueline R. Ward; Kommireddy Vasu; Emily Deutschman; Dalia Halawani; Peter A. Larson; Dongmei Zhang; Belinda Willard; Paul L. Fox; John V. Moran; Michelle S. Longw...
• Keywords: Adenosine Triphosphatases; Protein Synthesis Inhibitors; 0301 basic medicine; Retroelements; Genome, Human; Nuclear Proteins; Cell Cycle Proteins; Epithelial Cells; Interferon-Stimulated Gene Factor 3; QH426-470; 3. Good health; DNA-Binding Proteins; Interferon-gamma; 03 medical and health sciences; Long Interspersed Nucleotide Elements; Multiprotein Complexes; Genetics; Humans; RNA, Messenger; Research Article; Protein Binding

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.