Bridge RNAs direct modular and programmable recombination of target and donor DNA.

Autor: Durrant MG; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA., Perry NT; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Berkeley, CA, USA., Pai JJ; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA., Jangid AR; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA., Athukoralage JS; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA., Hiraizumi M; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., McSpedon JP; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA., Pawluk A; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA., Nishimasu H; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Structural Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.; Inamori Research Institute for Science, 620 Suiginya-cho, Shimogyo-ku, Kyoto 600-8411, Japan.; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan., Konermann S; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA.; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA., Hsu PD; Arc Institute, 3181 Porter Drive, Palo Alto, CA 94304, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.; Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 26. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1101/2024.01.24.577089
Abstrakt: Genomic rearrangements, encompassing mutational changes in the genome such as insertions, deletions, or inversions, are essential for genetic diversity. These rearrangements are typically orchestrated by enzymes involved in fundamental DNA repair processes such as homologous recombination or in the transposition of foreign genetic material by viruses and mobile genetic elements (MGEs). We report that IS110 insertion sequences, a family of minimal and autonomous MGEs, express a structured non-coding RNA that binds specifically to their encoded recombinase. This bridge RNA contains two internal loops encoding nucleotide stretches that base-pair with the target DNA and donor DNA, which is the IS110 element itself. We demonstrate that the target-binding and donor-binding loops can be independently reprogrammed to direct sequence-specific recombination between two DNA molecules. This modularity enables DNA insertion into genomic target sites as well as programmable DNA excision and inversion. The IS110 bridge system expands the diversity of nucleic acid-guided systems beyond CRISPR and RNA interference, offering a unified mechanism for the three fundamental DNA rearrangements required for genome design.
Databáze: MEDLINE