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MOV10 RNA helicase is a potent inhibitor of retrotransposition in cells.

Goodier JL, Cheung LE, Kazazian HH - PLoS Genet. (2012)

Bottom Line: However, unlike MOV10, these other helicases do not strongly inhibit retrotransposition, an activity dependent upon intact helicase domains.Therefore, the host has evolved defense mechanisms to protect against retrotransposition, an arsenal we are only beginning to understand.With homologs in other vertebrates, insects, and plants, MOV10 may represent an ancient and innate form of immunity against both infective viruses and endogenous retroelements.

View Article: PubMed Central - PubMed

Affiliation: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jgoodier@jhmi.edu

ABSTRACT
MOV10 protein, a putative RNA helicase and component of the RNA-induced silencing complex (RISC), inhibits retrovirus replication. We show that MOV10 also severely restricts human LINE1 (L1), Alu, and SVA retrotransposons. MOV10 associates with the L1 ribonucleoprotein particle, along with other RNA helicases including DDX5, DHX9, DDX17, DDX21, and DDX39A. However, unlike MOV10, these other helicases do not strongly inhibit retrotransposition, an activity dependent upon intact helicase domains. MOV10 association with retrotransposons is further supported by its colocalization with L1 ORF1 protein in stress granules, by cytoplasmic structures associated with RNA silencing, and by the ability of MOV10 to reduce endogenous and ectopic L1 expression. The majority of the human genome is repetitive DNA, most of which is the detritus of millions of years of accumulated retrotransposition. Retrotransposons remain active mutagens, and their insertion can disrupt gene function. Therefore, the host has evolved defense mechanisms to protect against retrotransposition, an arsenal we are only beginning to understand. With homologs in other vertebrates, insects, and plants, MOV10 may represent an ancient and innate form of immunity against both infective viruses and endogenous retroelements.

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Ectopically expressed and endogenous MOV10 closely colocalizes with L1 ORF1p in multiple cell lines.(A) EGFP-tagged ORF1p colocalizes with V5-tagged MOV10 in the cytoplasm and foci of 293T cells. (B) A mutation in the RRM RNA-binding domain of EGFP-ORF1p diminishes, but does not abolish, colocalization with MOV10 in cytoplasmic foci. (C) EGFP-ORF1p colocalizes with endogenous MOV10 in cytoplasmic granules of 2102Ep cells. (D) Endogenous ORF1p extensively colocalizes with RFP-tagged MOV10 in 2102Ep cells. (E) In 293T cells mouse mMOV10L is present in some, but not all ORF1p-marked cytoplasmic bodies, and significantly less often than MOV10. Scale bar: 10 µm.
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pgen-1002941-g002: Ectopically expressed and endogenous MOV10 closely colocalizes with L1 ORF1p in multiple cell lines.(A) EGFP-tagged ORF1p colocalizes with V5-tagged MOV10 in the cytoplasm and foci of 293T cells. (B) A mutation in the RRM RNA-binding domain of EGFP-ORF1p diminishes, but does not abolish, colocalization with MOV10 in cytoplasmic foci. (C) EGFP-ORF1p colocalizes with endogenous MOV10 in cytoplasmic granules of 2102Ep cells. (D) Endogenous ORF1p extensively colocalizes with RFP-tagged MOV10 in 2102Ep cells. (E) In 293T cells mouse mMOV10L is present in some, but not all ORF1p-marked cytoplasmic bodies, and significantly less often than MOV10. Scale bar: 10 µm.

Mentions: Meister et al. [10] demonstrated colocalization of MOV10 with AGO1 and AGO2, proteins that concentrate in PBs together with miRNAs and other components of the RNAi pathway [42]–[44]. Furthermore, Gallois-Montbrun et al. [13] reported that APOBEC3G and associated MOV10 colocalize in PBs of unstressed and in SGs of stressed cells. Contrarily, El Messaoudi-Aubert et al. [45] reported endogeous MOV10 to be mostly nuclear. In agreement with Sim et al. [46], we found MOV10 protein in unstressed cells to be predominantly cytoplasmic, mirroring the distribution of L1 ORF1p (Figure 2A and 2D).


MOV10 RNA helicase is a potent inhibitor of retrotransposition in cells.

Goodier JL, Cheung LE, Kazazian HH - PLoS Genet. (2012)

Ectopically expressed and endogenous MOV10 closely colocalizes with L1 ORF1p in multiple cell lines.(A) EGFP-tagged ORF1p colocalizes with V5-tagged MOV10 in the cytoplasm and foci of 293T cells. (B) A mutation in the RRM RNA-binding domain of EGFP-ORF1p diminishes, but does not abolish, colocalization with MOV10 in cytoplasmic foci. (C) EGFP-ORF1p colocalizes with endogenous MOV10 in cytoplasmic granules of 2102Ep cells. (D) Endogenous ORF1p extensively colocalizes with RFP-tagged MOV10 in 2102Ep cells. (E) In 293T cells mouse mMOV10L is present in some, but not all ORF1p-marked cytoplasmic bodies, and significantly less often than MOV10. Scale bar: 10 µm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3475670&req=5

pgen-1002941-g002: Ectopically expressed and endogenous MOV10 closely colocalizes with L1 ORF1p in multiple cell lines.(A) EGFP-tagged ORF1p colocalizes with V5-tagged MOV10 in the cytoplasm and foci of 293T cells. (B) A mutation in the RRM RNA-binding domain of EGFP-ORF1p diminishes, but does not abolish, colocalization with MOV10 in cytoplasmic foci. (C) EGFP-ORF1p colocalizes with endogenous MOV10 in cytoplasmic granules of 2102Ep cells. (D) Endogenous ORF1p extensively colocalizes with RFP-tagged MOV10 in 2102Ep cells. (E) In 293T cells mouse mMOV10L is present in some, but not all ORF1p-marked cytoplasmic bodies, and significantly less often than MOV10. Scale bar: 10 µm.
Mentions: Meister et al. [10] demonstrated colocalization of MOV10 with AGO1 and AGO2, proteins that concentrate in PBs together with miRNAs and other components of the RNAi pathway [42]–[44]. Furthermore, Gallois-Montbrun et al. [13] reported that APOBEC3G and associated MOV10 colocalize in PBs of unstressed and in SGs of stressed cells. Contrarily, El Messaoudi-Aubert et al. [45] reported endogeous MOV10 to be mostly nuclear. In agreement with Sim et al. [46], we found MOV10 protein in unstressed cells to be predominantly cytoplasmic, mirroring the distribution of L1 ORF1p (Figure 2A and 2D).

Bottom Line: However, unlike MOV10, these other helicases do not strongly inhibit retrotransposition, an activity dependent upon intact helicase domains.Therefore, the host has evolved defense mechanisms to protect against retrotransposition, an arsenal we are only beginning to understand.With homologs in other vertebrates, insects, and plants, MOV10 may represent an ancient and innate form of immunity against both infective viruses and endogenous retroelements.

View Article: PubMed Central - PubMed

Affiliation: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jgoodier@jhmi.edu

ABSTRACT
MOV10 protein, a putative RNA helicase and component of the RNA-induced silencing complex (RISC), inhibits retrovirus replication. We show that MOV10 also severely restricts human LINE1 (L1), Alu, and SVA retrotransposons. MOV10 associates with the L1 ribonucleoprotein particle, along with other RNA helicases including DDX5, DHX9, DDX17, DDX21, and DDX39A. However, unlike MOV10, these other helicases do not strongly inhibit retrotransposition, an activity dependent upon intact helicase domains. MOV10 association with retrotransposons is further supported by its colocalization with L1 ORF1 protein in stress granules, by cytoplasmic structures associated with RNA silencing, and by the ability of MOV10 to reduce endogenous and ectopic L1 expression. The majority of the human genome is repetitive DNA, most of which is the detritus of millions of years of accumulated retrotransposition. Retrotransposons remain active mutagens, and their insertion can disrupt gene function. Therefore, the host has evolved defense mechanisms to protect against retrotransposition, an arsenal we are only beginning to understand. With homologs in other vertebrates, insects, and plants, MOV10 may represent an ancient and innate form of immunity against both infective viruses and endogenous retroelements.

Show MeSH
Related in: MedlinePlus