{"doi":"10.1016/j.molcel.2025.11.019","title":"Phage-encoded small RNA hijacks host replication machinery to support the phage lytic cycle","abstract":"Bacteriophages (phages) are major drivers of bacterial population dynamics, yet the significance of post-transcriptional regulation during infection remains largely unexplored. Central to this regulatory layer are small RNAs (sRNAs), which regulate target mRNAs via base-pairing, typically facilitated by RNA chaperones such as Hfq. Here, we applied RNA interaction by ligation and sequencing (RIL-seq) to comprehensively map the in vivo RNA-RNA interaction network in Escherichia coli during phage lambda infection. This analysis revealed extensive reprogramming of E. coli-E. coli interactions, phage-specific lambda-lambda interactions, and interkingdom interactions between phage and host RNAs. Among these, we identified a phage-encoded sRNA, phage replication enhancer sRNA (PreS), embedded within the early left operon. PreS regulates essential host genes, including dnaN, which encodes the DNA polymerase β sliding clamp. This regulation enhances DNA replication and fine-tunes the phage lytic cycle. These findings uncover an RNA-level regulatory layer in phage-host interactions and demonstrate how a phage-encoded sRNA can hijack host replication machinery to optimize infection.","journal":"Molecular Cell","year":2025,"id":513628,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1375431,"name":"Raneem Nashef","orcid":null,"position":1,"is_corresponding":false},{"id":1375432,"name":"R WASSERMAN","orcid":null,"position":2,"is_corresponding":false},{"id":1375433,"name":"Tamar Noy","orcid":null,"position":3,"is_corresponding":false},{"id":1375434,"name":"Susan Born","orcid":null,"position":4,"is_corresponding":false},{"id":675643,"name":"Tianyou Yao","orcid":"0000-0003-4011-198X","position":5,"is_corresponding":false},{"id":625688,"name":"Yuncong Geng","orcid":"0000-0002-9998-7890","position":6,"is_corresponding":false},{"id":1375435,"name":"Hila Rotbard","orcid":null,"position":7,"is_corresponding":false},{"id":1375436,"name":"Adi Levkowitz","orcid":null,"position":8,"is_corresponding":false},{"id":1224729,"name":"Yotam Kaufman","orcid":null,"position":9,"is_corresponding":false},{"id":509996,"name":"Ido Golding","orcid":"0000-0002-4308-4959","position":10,"is_corresponding":false},{"id":340003,"name":"Sahar Melamed","orcid":"0000-0003-1360-1297","position":11,"is_corresponding":false},{"id":1065289,"name":"Aviezer Silverman","orcid":null,"position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T02:48:17.908238Z","pmid":"41418758","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":[]}