TY - JOUR
T1 - Bacterial Retrons Function In Anti-Phage Defense
AU - Millman, Adi
AU - Bernheim, Aude
AU - Stokar-Avihail, Avigail
AU - Fedorenko, Taya
AU - Voichek, Maya
AU - Leavitt, Azita
AU - Oppenheimer-Shaanan, Yaara
AU - Sorek, Rotem
N1 - We thank the Sorek laboratory members for comments on earlier versions of this manuscript. We also thank Hyeim Jung for providing us with a protocol for msDNA isolation. A.M. was supported by a fellowship from the Ariane de Rothschild Women Doctoral Program and, in part, by the Israeli Council for Higher Education via the Weizmann Data Science Research Center . A.B. is the recipient of a European Molecular Biology Organization (EMBO) Long Term Fellowship ( EMBO ALTF 186-2018 ). R.S. was supported, in part, by the Israel Science Foundation (personal grant 1360/16 ), the European Research Council ( ERC-CoG 681203 ), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine , the Minerva Foundation with funding from the Federal German Ministry for Education and Research , and the Knell Family Center for Microbiology . Author contributions - A.M., A.B., and A.S.-A. led the study and performed all analyses and experiments unless otherwise indicated. A.M. performed the computational analyses. A.B. and A.S.-A. performed the experimental assays and their analysis. Y.O.-S. performed the microscopy analysis that appears in Figure 4B. T.F. assisted with isolation of mutant phages that appear in Figure 5A and Table S2. M.V. performed RNA-seq analysis for Paenibacillus polymyxa that appears in Figure 1D. A.L. performed plaque assays that appear in Figure 1C. R.S. supervised the study and wrote the paper together with the team.
PY - 2020/12/10
Y1 - 2020/12/10
N2 - Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA (ncRNA). The RT uses the ncRNA as template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. We report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the ncRNA, and an effector protein. We examined multiple retron systems and show that they confer defense against a broad range of phages via abortive infection. Focusing on retron Ec48, we show evidence that it “guards” RecBCD, a complex with central anti-phage functions in bacteria. Inhibition of RecBCD by phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed.
AB - Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA (ncRNA). The RT uses the ncRNA as template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. We report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the ncRNA, and an effector protein. We examined multiple retron systems and show that they confer defense against a broad range of phages via abortive infection. Focusing on retron Ec48, we show evidence that it “guards” RecBCD, a complex with central anti-phage functions in bacteria. Inhibition of RecBCD by phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed.
UR - http://www.scopus.com/inward/record.url?scp=85096145403&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.09.065
DO - 10.1016/j.cell.2020.09.065
M3 - مقالة
C2 - 33157039
SN - 0092-8674
VL - 183
SP - 1551
EP - 1561
JO - Cell
JF - Cell
IS - 6
ER -