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Self versus non-self discrimination during CRISPR RNA-directed immunity
Open accessAbstract
All immune systems must distinguish self from non-self to repel invaders without inducing autoimmunity. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci protect bacteria and archaea from invasion by phage and plasmid DNA through a genetic interference pathway. CRISPR loci are present in ∼40% and ∼90% of sequenced bacterial and archaeal genomes, respectively, and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations. Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats. Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes that collectively encode >40 families of proteins involved in adaptation and interference. CRISPR loci encode small CRISPR RNAs (crRNAs) that contain a full spacer flanked by partial repeat sequences. CrRNA spacers are thought to identify targets by direct Watson–Crick pairing with invasive ‘protospacer’ DNA, but how they avoid targeting the spacer DNA within the encoding CRISPR locus itself is unknown. Here we have defined the mechanism of CRISPR self/non-self discrimination. In Staphylococcus epidermidis, target/crRNA mismatches at specific positions outside of the spacer sequence license foreign DNA for interference, whereas extended pairing between crRNA and CRISPR DNA repeats prevents autoimmunity. Hence, this CRISPR system uses the base-pairing potential of crRNAs not only to specify a target, but also to spare the bacterial chromosome from interference. Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways.
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Cites
Sorting of protein a to the staphylococcal cell wall
Schneewind, O., Model, P., & Fischetti, V. A. (1992) · Cell · doi:10.1016/0092-8674(92)90101-h · Cited by 552
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Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
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
RNA-guided editing of bacterial genomes using CRISPR-Cas systems
Jiang, W., Bikard, D., Cox, D., Zhang, F., & Marraffini, L. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2508 · Cited by 2,429
C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector
Abudayyeh, O. O., Gootenberg, J. S., Konermann, S., Joung, J., Slaymaker, I. M., Cox, D. B. T., Shmakov, S., Makarova, K. S., Semenova, E., Minakhin, L., et al. (2016) · Science · doi:10.1126/science.aaf5573 · Cited by 2,336
CRISPR–Cas9 Structures and Mechanisms
Jiang, F., & Doudna, J. A. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-062215-010822 · Cited by 2,029
RNA-guided genetic silencing systems in bacteria and archaea
Wiedenheft, B., Sternberg, S. H., & Doudna, J. A. (2012) · Nature · doi:10.1038/nature10886 · Cited by 1,851
DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
Sternberg, S. H., Redding, S., Jinek, M., Greene, E. C., & Doudna, J. A. (2014) · Nature · doi:10.1038/nature13011 · Cited by 1,822
CRISPR-Cas guides the future of genetic engineering
Knott, G. J., & Doudna, J. A. (2018) · Science · doi:10.1126/science.aat5011 · Cited by 1,410
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P. (2020) · Science · doi:10.1126/science.aba8853 · Cited by 1,233
Cas9 as a versatile tool for engineering biology
Mali, P., Esvelt, K. M., & Church, G. M. (2013) · Nature Methods · doi:10.1038/nmeth.2649 · Cited by 1,197
Biology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering
Wright, A. V., Nuñez, J. K., & Doudna, J. A. (2016) · Cell · doi:10.1016/j.cell.2015.12.035 · Cited by 989
CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea
Marraffini, L. A., & Sontheimer, E. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2749 · Cited by 919
Self-citationCRISPR-mediated adaptive immune systems in bacteria and archaea
Sorek, R., Lawrence, C. M., & Wiedenheft, B. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-072911-172315 · Cited by 668
Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system
Datsenko, K. A., Pougach, K., Tikhonov, A., Wanner, B. L., Severinov, K., & Semenova, E. (2012) · Nature Communications · doi:10.1038/ncomms1937 · Cited by 561
The CRISPR-Cas immune system: Biology, mechanisms and applications
Rath, D., Amlinger, L., Rath, A., & Lundgren, M. (2015) · Biochimie · doi:10.1016/j.biochi.2015.03.025 · Cited by 471
Small molecules enhance CRISPR genome editing in pluripotent stem cells
Yu, C., Liu, Y., Ma, T., Liu, K., Xu, S., Zhang, Y., Liu, H., La Russa, M., Xie, M., Ding, S., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.01.003 · Cited by 455
CRISPR-Cas: biology, mechanisms and relevance
Hille, F., & Charpentier, E. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0496 · Cited by 442
Co-transcriptional DNA and RNA Cleavage during Type III CRISPR-Cas Immunity
Samai, P., Pyenson, N., Jiang, W., Goldberg, G. W., Hatoum-Aslan, A., & Marraffini, L. A. (2015) · Cell · doi:10.1016/j.cell.2015.04.027 · Cited by 426
Self-citationKazlauskiene, M., Tamulaitis, G., Kostiuk, G., Venclovas, Č., & Siksnys, V. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.024 · Cited by 265
Horizontal gene transfer in human pathogens
Juhas, M. (2015) · Critical Reviews in Microbiology · doi:10.3109/1040841x.2013.804031 · Cited by 222
Xiao, Y., Luo, M., Hayes, R. P., Kim, J., Ng, S., Ding, F., Liao, M., & Ke, A. (2017) · Cell · doi:10.1016/j.cell.2017.06.012 · Cited by 208
Structural basis for promiscuous PAM recognition in type I–E Cascade from E. coli
Hayes, R. P., Xiao, Y., Ding, F., van Erp, P. B. G., Rajashankar, K., Bailey, S., Wiedenheft, B., & Ke, A. (2016) · Nature · doi:10.1038/nature16995 · Cited by 187
Hatoum-Aslan, A., Maniv, I., & Marraffini, L. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112832108 · Cited by 185
Self-citationCRISPR-Based Technologies: Impact of RNA-Targeting Systems
Terns, M. P. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.09.018 · Cited by 168
Type III CRISPR-Cas immunity: major differences brushed aside
Tamulaitis, G., Venclovas, Č., & Siksnys, V. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2016.09.012 · Cited by 126
Kaster, A.-K., Goenrich, M., Seedorf, H., Liesegang, H., Wollherr, A., Gottschalk, G., & Thauer, R. K. (2011) · Archaea · doi:10.1155/2011/973848 · Cited by 134
Advances in CRISPR-Cas systems for RNA targeting, tracking and editing
Wang, F., Wang, L., Zou, X., Duan, S., Li, Z., Deng, Z., Luo, J., Lee, S. Y., & Chen, S. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.03.016 · Cited by 128
Archaeal CRISPR-based immune systems: exchangeable functional modules
Garrett, R. A., Vestergaard, G., & Shah, S. A. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.08.002 · Cited by 98
Horii, T., Tamura, D., Morita, S., Kimura, M., & Hatada, I. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141019774 · Cited by 90
Silas, S., Makarova, K. S., Shmakov, S., Páez-Espino, D., Mohr, G., Liu, Y., Davison, M., Roux, S., Krishnamurthy, S. R., Fu, B. X. H., et al. (2017) · mBio · doi:10.1128/mbio.00897-17 · Cited by 62
Structural basis of CRISPR-Cas Type III prokaryotic defence systems
Molina, R., Sofos, N., & Montoya, G. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.06.010 · Cited by 48
Genome expansion by a CRISPR trimmer-integrase
Wang, J. Y., Tuck, O. T., Skopintsev, P., Soczek, K. M., Li, G., Al-Shayeb, B., Zhou, J., & Doudna, J. A. (2023) · Nature · doi:10.1038/s41586-023-06178-2 · Cited by 33
Guo, T., Zheng, F., Zeng, Z., Yang, Y., Li, Q., She, Q., & Han, W. (2019) · RNA Biology · doi:10.1080/15476286.2019.1642725 · Cited by 11
Structural insights into Cas9-mediated prespacer selection in CRISPR-Cas adaptation
Gaizauskaite, U., Tamulaitiene, G., Silanskas, A., Gasiunas, G., Siksnys, V., & Sasnauskas, G. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.01.022 · Cited by 2
Metadata
- Authors
- Marraffini, L. A., & Sontheimer, E. J.
- Venue
- Nature
- Published
- 2010-01
- Volume
- 463
- Issue
- 7280
- Pages
- 568-571
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2039731535
- Cited by
- 637
- References
- 1
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- green
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