吸收外源DNA的細(xì)菌和古細(xì)菌配備有宿主免疫系統(tǒng)，該系統(tǒng)能識(shí)別和清除外來(lái)DNA,。其中一個(gè)這樣的系統(tǒng)是由CRISPR基因調(diào)控的,，它們編碼小RNA（crRNA）。CRISPR位點(diǎn)由重復(fù)序列和間隔序列組成,。當(dāng)crRNA間隔序列與互補(bǔ)性的入侵DNA成對(duì)時(shí),，它便被標(biāo)記為要清除掉。
Luciano Marraffini 和 Erik Sontheimer解決了以下問(wèn)題：CRISPR位點(diǎn)本身內(nèi)的間隔DNA怎樣不被當(dāng)成外來(lái)的；間隔DNA之外的序列能夠與crRNA完美配對(duì),，而入侵DNA則無(wú)法匹配,。這種類(lèi)型的差異互補(bǔ)性可能是很多自我/非自我識(shí)別（所有免疫系統(tǒng)中的一個(gè)關(guān)鍵功能）的機(jī)制,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 463, 568-571 (28 January 2010) | doi:10.1038/nature08703
Self versus non-self discrimination during CRISPR RNA-directed immunity
Luciano A. Marraffini1 & Erik J. Sontheimer1
1 Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, Illinois 60208, USA
2 Correspondence to: Luciano A. Marraffini1Erik J. Sontheimer1 Correspondence and requests for materials should be addressed to L.A.M. and E.J.S.
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 pathway1, 2, 3, 4, 5, 6, 7, 8, 9. CRISPR loci are present in ~40% and ~90% of sequenced bacterial and archaeal genomes, respectively10, and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations1, 11, 12, 13. Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats1, 2, 3, 4, 5, 6, 7, 8, 9. Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes14, 15, 16 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 sequences2, 17, 18, 19. CrRNA spacers are thought to identify targets by direct Watson–Crick pairing with invasive ‘protospacer’ DNA2, 3, 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.
