MxB inhibits long interspersed element type 1 retrotransposition

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.

Ribonucleoprotein condensation driven by retrotransposon LINE-1 sustains RNA integrity and translation in mouse spermatocytes

“…Immunofluorescence and immunogold labeling show that ORF1p accumulates in LBs at exceptionally high levels (this work and 46 ). Prior studies in cultured cells have reported L1 association with SGs and their contribution to cellular defenses against L1 17,37,38,[76][77][78] . Meanwhile, L1 localization to PBs was reported only sporadically 79 .…”

Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response

“…Immunofluorescence and immunogold labeling show that ORF1p accumulates in LBs at exceptionally high levels (this work and [45]). Prior studies in cultured cells have reported L1 association with SGs and their contribution to cellular defenses against L1 [17,36,37,[78][79][80]. Meanwhile, L1 localization to PBs was reported only sporadically [81].…”

Ribonucleoprotein Granules: Between Stress and Transposable Elements

“…Given the function of ZAP in the destabilization of L1 RNAs and retrotransposition events, SG might be the cellular compartment involved in RNA metabolism to limit the stability of L1 RNAs and/or inhibit translation. Myxovirus resistance protein B (MxB), another interferonstimulated gene, also restricts L1 retrotransposition by enhancing the sequestration of ORF1p to G3BP1-containing cytoplasmic granules [105]. As MxB inhibits the nuclear import of HIV-1 and herpesvirus [106], the sequestration of L1 RNPs into SG might prevent the accession of L1 RNPs to the nucleus for their reverse transcription.…”