MxB inhibits long interspersed element type 1 retrotransposition

PLoS Genet. 2022 Feb 16;18(2):e1010034. doi: 10.1371/journal.pgen.1010034. eCollection 2022 Feb.

Abstract

Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism
  • Cytoplasmic Granules / metabolism
  • DNA Helicases / genetics
  • Deoxyribonuclease I / genetics*
  • Deoxyribonuclease I / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Long Interspersed Nucleotide Elements / genetics
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • RNA Helicases / genetics
  • RNA Recognition Motif Proteins / genetics
  • Retroelements

Substances

  • Myxovirus Resistance Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • Retroelements
  • Deoxyribonuclease I
  • LINE-1 endonuclease, human
  • DNA Helicases
  • RNA Helicases

Grants and funding

This study was supported by funds from CAMS Innovation Fund for Medical Sciences (CIFMS 2021-1-I2M-038) to F.G., from the National Key Plan for Scientific Research and Development of China (2018YFE0107600 and 2020YFA0707600) to F. G., from the Ministry of Science and Technology of China (2018ZX10301408-003) to F.G., from the National Natural Science Foundation of China (82072288) to F. G., from the Canadian Institutes of Health Research (CCI-132561) to C.L. and from the CAMS general fund (2019-RC-HL-012) to F. G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.