CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.
The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this defense. Upon detecting foreign DNA, typically from viruses, Cas proteins recognize specific sequences known as Protospacer Adjacent Motifs (PAMs). These motifs serve as indicators that distinguish invasive DNA from self-DNA. Once identified, the Cas complex excises a segment of the invader’s DNA, referred to as a protospacer and integrates it into the host genome within the CRISPR array. This array comprises short palindromic repeats interspersed with unique spacers derived from past invaders, thereby creating a molecular record of prior infections.
The CRISPR locus is subsequently transcribed into a long precursor RNA called pre-crRNA. This molecule is processed by RNase III and accessory Cas proteins into smaller CRISPR RNAs (crRNAs), each consisting of a single spacer-repeat unit. These crRNAs are critical for guiding the immune response during subsequent infections.
Upon reinfection by the same virus, the crRNA forms a complex with a Cas protein, typically Cas9 in many systems. This crRNA-Cas complex scans the invading DNA for a sequence complementary to the crRNA spacer. If a match is found adjacent to a PAM, the Cas protein cleaves the viral DNA at the target site, thereby halting the infection. The requirement for a PAM ensures that the CRISPR system does not target the host’s own genome, preserving cellular integrity.
Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR, together with CRISPR-associated Cas proteins, function as an adaptive immune system in bacteria and archaea against viruses and foreign genetic elements.
Once viral DNA is inside the cell, Cas proteins recognize the Protospacer Adjacent Motif or PAM, excise the protospacer segment from the viral genome, and insert it into the CRISPR array.
The CRISPR array stores viral DNA fragments as spacers between palindromic repeats, serving as a genetic memory to recognize past infections.
The CRISPR array is transcribed into pre-crRNA, which pairs with tracrRNA. RNase III and Cas9 process the duplex into crRNAs, each carrying one spacer and repeat fragments.
When the virus re-infects, the Cas-crRNA complex scans for a match.
The Cas protein cleaves the viral DNA upon matching, neutralizing the infection.
The PAM enhances the specificity of this defense by ensuring that Cas proteins target only foreign DNA and not the bacterium’s own CRISPR array.
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