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Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes

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dc.contributor.authorMoldovan, John B
dc.contributor.authorKopera, Huira C
dc.contributor.authorLiu, Ying
dc.contributor.authorGarcia-Canadas, Marta
dc.contributor.authorCatalina, Purificacion
dc.contributor.authorLeone, Paola E
dc.contributor.authorSanchez, Laura
dc.contributor.authorKitzman, Jacob O
dc.contributor.authorKidd, Jeffrey M
dc.contributor.authorGarcia-Perez, Jose Luis
dc.contributor.authorMoran, John V
dc.date.accessioned2024-10-10T13:30:17Z
dc.date.available2024-10-10T13:30:17Z
dc.date.issued2024
dc.description.abstractAlu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1) ORF2-encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition. Human Alu elements retrotranspose efficiently in HeLa-HA and HeLa-CCL2 (Alu-permissive) strains, but not in HeLa-JVM or HeLa-H1 (Alu-nonpermissive) strains. A similar pattern of retrotransposition was observed for other 7SL RNA-derived SINEs and tRNA-derived SINEs. In contrast, mammalian LINE-1s, a zebrafish LINE, a human SINE-VNTR-Alu (SVA) element, and an L1 ORF1-containing mRNA can retrotranspose in all four HeLa strains. Using an in vitro reverse transcriptase-based assay, we show that Alu RNAs associate with ORF2p and are converted into cDNAs in both Alu-permissive and Alu-nonpermissive HeLa strains, suggesting that 7SL- and tRNA-derived SINEs use strategies to 'hijack' L1 ORF2p that are distinct from those used by SVA elements and ORF1-containing mRNAs. These data further suggest ORF2p associates with the Alu RNA poly(A) tract in both Alu-permissive and Alu-nonpermissive HeLa strains, but that Alu retrotransposition is blocked after this critical step in Alu-nonpermissive HeLa strains.
dc.identifier.citationMoldovan JB, Kopera HC, Liu Y, Garcia-Canadas M, Catalina P, Leone PE, Sanchez L, Kitzman JO, Kidd JM, Garcia-Perez JL, Moran JV. Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes. Nucleic Acids Res. 2024 Jul 22;52(13):7761-7779. doi: 10.1093/nar/gkae448. PMID: 38850156; PMCID: PMC11260458.
dc.identifier.urihttp://biblioteca.solcaquito.org.ec:9997/handle/123456789/1679
dc.language.isoen
dc.titleVariable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes
dc.typeArticle
dspace.entity.typePublication
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