{"doi":"10.1093/nar/gkae448","title":"Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes","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 (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.","journal":"Nucleic Acids Research","year":2024,"id":442598,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":527075,"name":"Huira C. Kopera","orcid":"0000-0002-8347-5567","position":1,"is_corresponding":false},{"id":1256358,"name":"Ying Liu","orcid":"0000-0002-4631-0915","position":2,"is_corresponding":false},{"id":1256359,"name":"Marta García-Cañadas","orcid":"0000-0002-3805-179X","position":3,"is_corresponding":false},{"id":1256360,"name":"Purificación Catalina","orcid":"0000-0001-6544-3601","position":4,"is_corresponding":false},{"id":555765,"name":"Paola Leone","orcid":"0000-0003-3351-2275","position":5,"is_corresponding":false},{"id":400542,"name":"Laura Sánchez","orcid":"0000-0003-2243-6166","position":6,"is_corresponding":false},{"id":40413,"name":"Jacob O. Kitzman","orcid":"0000-0002-6145-882X","position":7,"is_corresponding":false},{"id":19567,"name":"Jeffrey M. Kidd","orcid":"0000-0002-9631-1465","position":8,"is_corresponding":false},{"id":400543,"name":"José L. García-Pérez","orcid":"0000-0002-8132-9849","position":9,"is_corresponding":false},{"id":557089,"name":"John V. Moran","orcid":"0000-0002-5308-4864","position":10,"is_corresponding":false},{"id":1035882,"name":"John B. Moldovan","orcid":"0000-0002-1703-734X","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:01:20.107161Z","pmid":"38850156","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}