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MxB inhibits long interspersed element type 1 retrotransposition
- Source :
- PLoS Genetics, Vol 18, Iss 2 (2022)
- Publication Year :
- 2021
-
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. Author summary Retrotransposons occupy more than 40% of human genome, and have co-evolved with humans for millions of years. Long interspersed element type 1 (LINE-1, or L1) is the only retrotransposon that is able to jump to a new locus. LINE-1 retrotransposition causes genome instability, and is associated with genetic diseases including autoimmune diseases and cancer. To suppress this genome toxicity caused by LINE-1, humans have developed multi-layered mechanisms to control LINE-1 activity. MxB has been previously shown to inhibit LINE-1 mobility, thus contributing to host restriction of LINE-1. Here, we further demonstrate that MxB effectively restricts LINE-1 retrotransposition by sequestering LINE-1 ribonucleoprotein (RNP) within the cytoplasmic stress granules, thus guards genome stability. Hence our data attribute the restriction function of MxB to sequestering LINE-1 RNP to stress granules.
- Subjects :
- Cell Nucleus
Myxovirus Resistance Proteins
Cancer Research
Retroelements
DNA Helicases
QH426-470
Cytoplasmic Granules
HEK293 Cells
Long Interspersed Nucleotide Elements
RNA Recognition Motif Proteins
Genetics
Deoxyribonuclease I
Humans
Poly-ADP-Ribose Binding Proteins
Molecular Biology
Genetics (clinical)
Ecology, Evolution, Behavior and Systematics
RNA Helicases
HeLa Cells
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 18
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS genetics
- Accession number :
- edsair.doi.dedup.....bfd4bb90cfb67e7dca0df935c0e72b4e