Bacterial immune defense system defies central DNA dogma

Amazing stuff!

"It’s among the most well-known rules in modern biology: Genetic information flows in one direction, from DNA to RNA to protein. But a recent discovery complicates and adds nuance to this so-called central dogma.

In a recently posted preprint, Columbia University researchers show that at least one species of bacteria, named Klebsiella pneumoniae, uses instructions for genes that lie outside of the genome, floating around in the cytoplasm. And, unlike most genes, these adrift genetic letters contain instructions that are not encoded in DNA, but rather RNA. Essentially, the flow of genetic information goes backward, from RNA to DNA, before it can go forward, from DNA to RNA to protein. The gene in Klebsiella pneumoniae encodes for an immune protein that’s activated once a virus infects the cell; this oddball setup appears to be part of an immune defense system that patrols the cell looking for viral invaders. ...
Bacteria have a diverse arsenal of viral defense systems. They include CRISPR-Cas9, which has garnered attention for its ability to deftly edit genomes. In bacteria, CRISPR-Cas9 allows foreign DNA to be spliced into the genome and expressed, offering a way for bacteria to remember past viral invaders so that they can quickly identify and destroy them when seen again. Another gene editing system gaining popularity, Prime editing, uses RNA and reverse transcriptase to create gene sequences. ...
Floating around in the cytoplasm were pieces of RNA shaped like hairpin loops, and bound to those RNA bits were reverse-transcriptase enzymes, which write DNA from RNA templates. These free-floating RNAs were being continuously transcribed by the enzymes in a seemingly endless loop that buzzed around the hairpin structure without stopping. ..."

From the abstract:

"Bacteria defend themselves from viral infection using diverse immune systems, many of which sense and target foreign nucleic acids. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this immune strategy by instead leveraging DNA synthesis, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems execute an unprecedented immunity mechanism that involves de novo gene synthesis via rolling-circle reverse transcription of a non-coding RNA (ncRNA). Unbiased profiling of RT-associated RNA and DNA ligands in DRT2-expressing cells revealed that reverse transcription generates concatenated cDNA repeats through programmed template jumping on the ncRNA. The presence of phage then triggers second-strand cDNA synthesis, leading to the production of long double-stranded DNA. Remarkably, this DNA product is efficiently transcribed, generating messenger RNAs that encode a stop codon-less, never-ending ORF (neo) whose translation causes potent growth arrest. Phylogenetic analyses and screening of diverse DRT2 homologs further revealed broad conservation of rolling-circle reverse transcription and Neo protein function. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation, and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA."

Bacterial defense system defies central DNA dogma | Journal Club | PNAS

De novo gene synthesis by an antiviral reverse transcriptase (open access)