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The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
Open accessAbstract
Tracing the origin of CRISPR-Cas: CRISPR-Cas systems have transformed genome editing and other biotechnologies; however, the broader origins and diversity of RNA-guided nucleases have largely remained unexplored. Altae-Tran et al . show that three distinct transposon-encoded proteins, IscB, IsrB, and TnpB, are naturally occurring, reprogrammable RNA-guided DNA nucleases (see the Perspective by Rousset and Sorek). In addition to identifying diverse guide-encoding mechanisms, the authors elucidate the evolutionary relationship between IsrB, IscB, and CRISPR-Cas9. Overall, these newly characterized systems, called OMEGA (for obligate mobile element–guided activity) systems, are found in all domains of life and may be harnessed for biotechnology development. —DJ
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“The IS200/IS605 family of MGEs spreads through “peel-and-paste” transposition catalyzed by the homodimeric transposase TnpA interacting with terminal hairpins at the left end (LE) and right end (RE) of the element.”
From Sequence modeling and design from molecular to genome scale with Evo (2024) · cites this paper as [68]
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“IS605 elements additionally contain an RNA-guided TnpB nuclease and a cognate ωRNA that bias the selfish inheritance of the transposable element (Fig. 4A) (66–69).”
From Sequence modeling and design from molecular to genome scale with Evo (2024) · cites this paper as [68]
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“The discovery of TnpB’s RNA-guided nuclease activity expands the toolkit available for genome editing, particularly in organisms where traditional CRISPR systems may not be as effective.”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Altae-Tran et al., 2021
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Citations
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
Katoh, K., & Standley, D. M. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst010 · Cited by 46,209
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889
(2008) · Journal of Machine Learning Research · Cited by 33,051
RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies
Stamatakis, A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu033 · Cited by 32,291
SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing
Bankevich, A., Nurk, S., Antipov, D., Gurevich, A. A., Dvorkin, M. V., Kulikov, A. S., Lesin, V. M., Nikolenko, S., Pham, S., Prjibelski, A. D., et al. (2012) · Journal of Computational Biology · doi:10.1089/cmb.2012.0021 · Cited by 26,312
BLAST+: architecture and applications
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., & Madden, T. L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-421 · Cited by 22,074
Silhouettes: A graphical aid to the interpretation and validation of cluster analysis
Rousseeuw, P. J. (1987) · Journal of Computational and Applied Mathematics · doi:10.1016/0377-0427(87)90125-7 · Cited by 21,392
ModelFinder: fast model selection for accurate phylogenetic estimates
Kalyaanamoorthy, S., Minh, B. Q., Wong, T. K. F., von Haeseler, A., & Jermiin, L. S. (2017) · Nature Methods · doi:10.1038/nmeth.4285 · Cited by 18,449
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era
Minh, B. Q., Schmidt, H. A., Chernomor, O., Schrempf, D., Woodhams, M. D., von Haeseler, A., & Lanfear, R. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa015 · Cited by 16,873
FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments
Price, M. N., Dehal, P. S., & Arkin, A. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009490 · Cited by 14,894
Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P., & Tyson, G. W. (2015) · Genome Research · doi:10.1101/gr.186072.114 · Cited by 12,496
UFBoot2: Improving the Ultrafast Bootstrap Approximation
Hoang, D. T., Chernomor, O., von Haeseler, A., Minh, B. Q., & Vinh, L. S. (2018) · Molecular Biology and Evolution · doi:10.1093/molbev/msx281 · Cited by 10,881
Pfam: The protein families database in 2021
Mistry, J., Chuguransky, S., Williams, L., Qureshi, M., Salazar, G. A., Sonnhammer, E. L. L., Tosatto, S. C. E., Paladin, L., Raj, S., Richardson, L. J., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa913 · Cited by 7,452
Accelerated Profile HMM Searches
Eddy, S. R. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002195 · Cited by 6,975
GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database
Chaumeil, P.-A., Mussig, A. J., Hugenholtz, P., & Parks, D. H. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz848 · Cited by 5,337
Lorenz, R., Bernhart, S. H., Höner zu Siederdissen, C., Tafer, H., Flamm, C., Stadler, P. F., & Hofacker, I. L. (2011) · Algorithms for Molecular Biology · doi:10.1186/1748-7188-6-26 · Cited by 5,098
MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets
Steinegger, M., & Söding, J. (2017) · Nature Biotechnology · doi:10.1038/nbt.3988 · Cited by 4,840
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., Volz, S. E., Joung, J., van der Oost, J., Regev, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.038 · Cited by 4,761
Self-citationInfernal 1.1: 100-fold faster RNA homology searches
Nawrocki, E. P., & Eddy, S. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt509 · Cited by 3,554
Gasiunas, G., Barrangou, R., Horvath, P., & Siksnys, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208507109 · Cited by 2,769
Density-Based Clustering Based on Hierarchical Density Estimates
Campello, R. J. G. B., Moulavi, D., & Sander, J. (2013) · Lecture Notes in Computer Science · doi:10.1007/978-3-642-37456-2_14 · Cited by 2,680
CRISPR RNA Maturation by Trans-Encoded Small RNA and Host Factor RNase III
Deltcheva, E., Chylinski, K., Sharma, C. M., Gonzales, K., Chao, Y., Pirzada, Z. A., Eckert, M. R., Vogel, J., & Charpentier, E. (2011) · Nature · doi:10.1038/nature09886 · Cited by 2,563
Improved microbial gene identification with GLIMMER
Delcher, A. L. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.23.4636 · Cited by 2,493
Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants
Makarova, K. S., Wolf, Y. I., Iranzo, J., Shmakov, S. A., Alkhnbashi, O. S., Brouns, S. J. J., Charpentier, E., Cheng, D., Haft, D. H., Horvath, P., et al. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0299-x · Cited by 2,445
Self-citationCrystal structure of Cas9 in complex with guide RNA and target DNA
Nishimasu, H., Ran, F. A., Hsu, P. D., Konermann, S., Shehata, S. I., Dohmae, N., Ishitani, R., Zhang, F., & Nureki, O. (2014) · Cell · doi:10.1016/j.cell.2014.02.001 · Cited by 2,306
Criscuolo, A., & Gribaldo, S. (2010) · BMC Evolutionary Biology · doi:10.1186/1471-2148-10-210 · Cited by 1,667
CRISPResso2 provides accurate and rapid genome editing sequence analysis
Clement, K., Rees, H. A., Canver, M. C., Gehrke, J. M., Farouni, R., Hsu, J. Y., Cole, M. A., Liu, D. R., Joung, J. K., Bauer, D. E., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0032-3 · Cited by 1,656
Structures of Cas9 endonucleases reveal RNA-mediated conformational activation
Jinek, M., Jiang, F., Taylor, D. W., Sternberg, S. H., Kaya, E., Ma, E., Anders, C., Hauer, M., Zhou, K., Lin, S., et al. (2014) · Science · doi:10.1126/science.1247997 · Cited by 1,230
Parallel Metropolis coupled Markov chain Monte Carlo for Bayesian phylogenetic inference
Altekar, G., Dwarkadas, S., Huelsenbeck, J. P., & Ronquist, F. (2004) · Bioinformatics · doi:10.1093/bioinformatics/btg427 · Cited by 1,149
HH-suite3 for fast remote homology detection and deep protein annotation
Steinegger, M., Meier, M., Mirdita, M., Vöhringer, H., Haunsberger, S. J., & Söding, J. (2019) · BMC Bioinformatics · doi:10.1186/s12859-019-3019-7 · Cited by 1,145
The Biology of CRISPR-Cas: Backward and Forward
Hille, F., Richter, H., Wong, S. P., Bratovič, M., Ressel, S., & Charpentier, E. (2018) · Cell · doi:10.1016/j.cell.2017.11.032 · Cited by 1,070
Bland, C., Ramsey, T. L., Sabree, F., Lowe, M., Brown, K., Kyrpides, N. C., & Hugenholtz, P. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-209 · Cited by 1,038
Rfam 14: expanded coverage of metagenomic, viral and microRNA families
Kalvari, I., Nawrocki, E. P., Ontiveros‐Palacios, N., Argasinska, J., Lamkiewicz, K., Marz, M., Griffiths‐Jones, S., Toffano‐Nioche, C., Gautheret, D., Zasha Weinberg, A., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1047 · Cited by 1,035
Diversity and evolution of class 2 CRISPR–Cas systems
Shmakov, S., Smargon, A., Scott, D., Cox, D., Pyzocha, N., Yan, W., Abudayyeh, O. O., Gootenberg, J. S., Makarova, K. S., Wolf, Y. I., et al. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.184 · Cited by 1,029
Self-citationCompact graphical representation of phylogenetic data and metadata with GraPhlAn
Asnicar, F., Weingart, G., Tickle, T. L., Huttenhower, C., & Segata, N. (2015) · PeerJ · doi:10.7717/peerj.1029 · Cited by 818
Bacterial insertion sequences: their genomic impact and diversity
Siguier, P., Gourbeyre, E., & Chandler, M. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12067 · Cited by 773
RNA-guided DNA insertion with CRISPR-associated transposases
Strecker, J., Ladha, A., Gardner, Z., Schmid-Burgk, J. L., Makarova, K. S., Koonin, E. V., & Zhang, F. (2019) · Science · doi:10.1126/science.aax9181 · Cited by 707
Self-citationTransposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration
Klompe, S. E., Vo, P. L. H., Halpin-Healy, T. S., & Sternberg, S. H. (2019) · Nature · doi:10.1038/s41586-019-1323-z · Cited by 632
TIGRFAMs: a protein family resource for the functional identification of proteins
Haft, D. H. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.41 · Cited by 495
A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs
Rivas, E., Clements, J., & Eddy, S. R. (2016) · Nature Methods · doi:10.1038/nmeth.4066 · Cited by 381
R2R - software to speed the depiction of aesthetic consensus RNA secondary structures
Weinberg, Z., & Breaker, R. R. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-3 · Cited by 287
Lockhart, P. J., Larkum, A., Steel, M. A., Waddell, P., & Penny, D. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.5.1930 · Cited by 240
GHOST: Recovering Historical Signal from Heterotachously Evolved Sequence Alignments
Crotty, S., Minh, B. Q., Bean, N. G., Holland, B. R., Tuke, J., Jermiin, L. S., & von Haeseler, A. (2019) · Systematic Biology · doi:10.1093/sysbio/syz051 · Cited by 206
A new set of highly efficient, tag-cleaving proteases for purifying recombinant proteins
Frey, S., & Görlich, D. (2014) · Journal of Chromatography A · doi:10.1016/j.chroma.2014.02.029 · Cited by 190
Development of CRISPR-Cas systems for genome editing and beyond
Zhang, F. (2019) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583519000052 · Cited by 188
Self-citationThe Prevalence and Impact of Model Violations in Phylogenetic Analysis
Naser-Khdour, S., Minh, B. Q., Zhang, W., Stone, E. A., & Lanfear, R. (2019) · Genome Biology and Evolution · doi:10.1093/gbe/evz193 · Cited by 188
Krupovìč, M., Makarova, K. S., Forterre, P., Prangishvili, D. A., & Koonin, E. V. (2014) · BMC Biology · doi:10.1186/1741-7007-12-36 · Cited by 187
Self-citationA catalogue of biochemically diverse CRISPR-Cas9 orthologs
Gasiūnas, G., Young, J. K., Karvelis, T., Kazlauskas, D., Urbaitis, T., Jasnauskaitė, M., Grusyte, M. M., Paulraj, S., Wang, P.-H., Hou, Z., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19344-1 · Cited by 181
Majorek, K. A., Dunin-Horkawicz, S., Steczkiewicz, K., Muszewska, A., Nowotny, M., Ginalski, K., & Bujnicki, J. M. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1414 · Cited by 174
Shmakov, S. A., Makarova, K. S., Wolf, Y. I., Severinov, K. V., & Koonin, E. V. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803440115 · Cited by 169
Self-citationKoonin, E. V. (2017) · Biology Direct · doi:10.1186/s13062-017-0177-2 · Cited by 153
Self-citationWeinberg, Z., Lünse, C. E., Corbino, K. A., Ames, T., Nelson, J. W., Roth, A., Perkins, K. R., Sherlock, M., & Breaker, R. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx699 · Cited by 148
Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis
Weinberg, Z., Perreault, J., Meyer, M. M., & Breaker, R. R. (2009) · Nature · doi:10.1038/nature08586 · Cited by 126
ISC, a Novel Group of Bacterial and Archaeal DNA Transposons That Encode Cas9 Homologs
Kapitonov, V. V., Makarova, K. S., & Koonin, E. V. (2015) · Journal of Bacteriology · doi:10.1128/jb.00783-15 · Cited by 120
Self-citationSriramachandran, A. M., Petrosino, G., Méndez-Lago, M., Schäfer, A. J., Batista-Nascimento, L. S., Zilio, N., & Ulrich, H. D. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.027 · Cited by 114
Homologues of bacterial TnpB_IS605 are widespread in diverse eukaryotic transposable elements
Bao, W., & Jurka, J. (2013) · Mobile DNA · doi:10.1186/1759-8753-4-12 · Cited by 111
CRISPRdisco: An Automated Pipeline for the Discovery and Analysis of CRISPR-Cas Systems
Crawley, A. B., Henriksen, J. R., & Barrangou, R. (2018) · The CRISPR Journal · doi:10.1089/crispr.2017.0022 · Cited by 97
Divergent copies of the large inverted repeat in the chloroplast genomes of ulvophycean green algae
Turmel, M., Otis, C., & Lemieux, C. (2017) · Scientific Reports · doi:10.1038/s41598-017-01144-1 · Cited by 82
GHOST: Recovering Historical Signal from Heterotachously-evolved Sequence AlignmentsPreprint
Crotty, S., Minh, B. Q., Bean, N. G., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/174789 · Cited by 81
The principles of guiding by RNA: chimeric RNA–protein enzymes
Hüttenhofer, A., & Schattner, P. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1855 · Cited by 57
Gomes‐Filho, J. V., Zaramela, L. S., Italiani, V. C. S., Baliga, N. S., Vêncio, R. Z. N., & Koide, T. (2015) · RNA Biology · doi:10.1080/15476286.2015.1019998 · Cited by 29
Schneider, A. (2020) · EMBO Reports · doi:10.15252/embr.202051918 · Cited by 17
Embedding to Reference t-SNE Space Addresses Batch Effects in Single-Cell ClassificationPreprint
Poličar, P. G., Stražar, M., & Zupan, B. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/671404 · Cited by 9
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Nguyen, E., Poli, M., Durrant, M. G., Kang, B., Katrekar, D., Li, D. B., Bartie, L. J., Thomas, A. W., King, S. H., Brixi, G., et al. (2024) · Science · doi:10.1126/science.ado9336 · Cited by 580
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Liu, C., Shi, Q., Huang, X., Koo, S., Kong, N., & Tao, W. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-023-00586-2 · Cited by 500
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Liu, G., Lin, Q., Jin, S., & Gao, C. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.002 · Cited by 422
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Metadata
- Authors
- Altae-Tran, H., Kannan, S., Demircioglu, F. E., Oshiro, R., Nety, S. P., McKay, L. J., Dlakić, M., Inskeep, W. P., Makarova, K. S., Macrae, R. K., Koonin, E. V., & Zhang, F.
- Affiliations
- Broad Institute (US)
- Montana State University (US)
- United States National Library of Medicine (US)
- Corresponding author
- Altae-Tran, Han
- Kannan, Soumya
- Zhang, Feng
- ORCID
- Venue
- Science
- Published
- 2021-10
- Volume
- 374
- Issue
- 6563
- Pages
- 57-65
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8929163
- OpenAlex
- W3198344223
- Cited by
- 407
- References
- 65
- Citations by year
- 2026: 78 · 2025: 92 · 2024: 102 · 2023: 77 · 2022: 42 · 2021: 16
- FWCI
- 18.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- Montana State University ScholarWorks (Montana State University) (submittedVersion)
- Funders
- National Science Foundation (1950770)
- U.S. Department of Energy
- Edward Mallinckrodt, Jr. Foundation
- Open Philanthropy Project
- Joint Genome Institute
- National Institutes of Health (5r01hg009761-06, HG009761, 1R01- HG009761)
- National Park Service
- National Heart, Lung, and Blood Institute (DP1HL141201)
- National Human Genome Research Institute (R01-HG009761)
- U.S. National Library of Medicine
- Division of Environmental Biology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- TnpB, RNA-guided endonuclease, genome editing, transposable elements, RNA-guided DNA cleavage
- MeSH terms
- CRISPR-Associated Protein 9, RNA, Guide, CRISPR-Cas Systems, Bacterial Proteins, DNA Transposable Elements, Endodeoxyribonucleases, Genetic Code, Genetic Variation, Conserved Sequence, Evolution, Molecular, RNA, Untranslated, CRISPR-Cas Systems, CRISPR-Associated Proteins
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