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

Moldovan, JB, Kopera, HC, Liu, Y et al. (2024). Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes . NUCLEIC ACIDS RESEARCH, 52(13), 7761-7779. 10.1093/nar/gkae448

cited authors

  • Moldovan, JB; Kopera, HC; Liu, Y; Garcia-Canadas, M; Catalina, P; Leone, PE; Sanchez, L; Kitzman, JO; Kidd, JM; Garcia-Perez, JL; Moran, JV

authors

abstract

  • Alu 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 (Alunonpermissive) 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.

publication date

  • July 22, 2024

published in

Digital Object Identifier (DOI)

start page

  • 7761

end page

  • 7779

volume

  • 52

issue

  • 13