The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases.

Autor:	Altae-Tran H; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Kannan S; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Demircioglu FE; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Oshiro R; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Nety SP; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., McKay LJ; Department of Land Resources and Environmental Sciences, Montana State University, Bozeman, MT 59717, USA.; Thermal Biology Institute, Montana State University, Bozeman, MT 59717, USA.; Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA., Dlakić M; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA., Inskeep WP; Department of Land Resources and Environmental Sciences, Montana State University, Bozeman, MT 59717, USA.; Thermal Biology Institute, Montana State University, Bozeman, MT 59717, USA., Makarova KS; National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA., Macrae RK; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Koonin EV; National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA., Zhang F; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2021 Oct; Vol. 374 (6563), pp. 57-65. Date of Electronic Publication: 2021 Sep 09.
DOI:	10.1126/science.abj6856
Abstrakt:	IscB proteins are putative nucleases encoded in a distinct family of IS200/IS605 transposons and are likely ancestors of the RNA-guided endonuclease Cas9, but the functions of IscB and its interactions with any RNA remain uncharacterized. Using evolutionary analysis, RNA sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells. We also demonstrate the RNA-guided nuclease activity of TnpB, another IS200/IS605 transposon-encoded protein and the likely ancestor of Cas12 endonucleases. This work reveals a widespread class of transposon-encoded RNA-guided nucleases, which we name OMEGA (obligate mobile element–guided activity), with strong potential for developing as biotechnologies.
Databáze:	MEDLINE
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