MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells

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.

The MOV10 Helicase Inhibits LINE-1 Mobility

“…1D), although compared with wild type MOV10, the inhibition activity of MOV10 (EQ) was markedly attenuated. Similar to our findings, Goodier et al (55) reported that similar mutations in the GKT and the DEAG motifs abolished anti-LINE-1 activity of MOV10. These results collectively indicate that the helicase motifs of MOV10 are required for suppressing the replication of LINE-1 and IAP.…”

“…studies (55)(56)(57). Because the transcription activity of LINE-1 promoter is not evidently affected by MOV10 (Fig.…”

“…Recent evidence showed that MOV10 co-localized with LINE-1 RNP in stress granules in the cytoplasmic (55). This raises the possibility that the above mutated GKT and DEAG motifs may alter the cytoplasmic localization of MOV10, consequently affecting its activity against LINE-1.…”

Stress out the LINEs

“…Goodier et al first reported the localization of LINE-1 RNP components with stress granule markers. 38 [24][25][26] co-localize with LINE-1 RNP in stress granules or P-bodies (Fig. 1).…”

“…[19][20][21][22][23] An RNA helicase MOV10 inhibits retrotransposition of LINE-1 by associating with LINE-1 RNP and diminishing LINE-1 RNA level. [24][25][26] A recent study by Goodier et al tested a panel of viral restriction factors and showed that many of them, including BST-2, ISG20, MAVS, Mx2 and ZAP, strongly reduce LINE-1 activity. 27 The anti-LINE-1 activity of ZAP was also reported by Moran group.…”