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Phage-triggered reverse transcription assembles a toxic repetitive gene from a noncoding RNA

Affiliations
  • 1Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 2Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 3McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 4Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 5Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 6Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • 7Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.

Published on:

August 29, 2024

Abstract

Reverse transcription has frequently been co-opted for cellular functions and in prokaryotes is associated with protection against viral infection, but the underlying mechanisms of defense are generally unknown. Here, we show that in the DRT2 defense system, the reverse transcriptase binds a neighboring pseudoknotted noncoding RNA. Upon bacteriophage infection, a template region of this RNA is reverse transcribed into an array of tandem repeats that reconstitute a promoter and open reading frame, allowing expression of a toxic repetitive protein and an abortive infection response. Biochemical reconstitution of this activity and cryo-electron microscopy provide a molecular basis for repeat synthesis. Gene synthesis from a noncoding RNA is a previously unknown mode of genetic regulation in prokaryotes.

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