Phage-encoded small RNA hijacks host replication machinery to support the phage lytic cycle
Aviezer Silverman, Raneem Nashef, R WASSERMAN, Tamar Noy, Susan Born, Tianyou Yao, Yuncong Geng, Hila Rotbard, Adi Levkowitz, Yotam Kaufman, Ido Golding, Sahar Melamed
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.