CRISPR is most commonly known as a set of gene editing tools - even showing up in TV shows and movies, recognized by the general public. While CRISPR is relatively new to researchers, to bacteria and archaea, it is an ancient adaptive immune system.
Though we often think of microbes as the targets of immune systems, they themselves face a number of threats, including viruses and other sources of foreign genetic material that could hijack their cells. CRISPR is just one of the defenses that bacteria and archaea use to fend off these attacks, but is of particular interest because it adapts to target new threats. Phages, which are viruses that infect bacteria and archaea, are a common target of CRISPR systems.
Bacteria and archaea with CRISPR systems build libraries of short genetic sequences from past invaders, and use CRISPR complexes to identify those invaders if they show up again. Matching genetic sequences are destroyed, preventing an infection.
CRISPR systems are diverse and several different types have been identified, but they have a number of common components.
The “library” of CRISPR systems is a DNA array that alternates between short repeat regions and “spacer” sequences that come from past invaders. The name CRISPR comes from an early description of these arrays: Clustered Regularly Interspaced Short Palindromic Repeats.
Genes that code for the proteins involved in CRISPR are called cas (CRISPR associated) genes, usually located near the CRISPR array.
The spacers in the CRISPR arrays are transcribed and processed into crRNAs that are each used to match a single spacer.
Invading genetic sequences are targeted and destroyed by CRISPR complexes. These complexes all contain at least one protein and a crRNA but are highly diverse, and different CRISPR systems are often distinguished by their complexes. In some systems the CRISPR complex has multiple protein subunits, while others have a single protein. Some also have additional components, such as the Type II CRISPR/Cas9 system’s tracrRNA.
In the Interference stage of the CRISPR process, the CRISPR complexes containing crRNA find and destroy nucleic acids that match the crRNA sequence. CRISPR systems are diverse, and the specific steps involved and the details of the process vary. For example, in some systems the CRISPR complex uses a single protein, while others have multiple protein subunits. The targets also vary - some systems target double-stranded DNA, others target RNA, and one type targets both RNA and DNA in a transcription-dependent process. To learn more about Interference in Type I and Type III systems, check out the entries below.
CRISPR systems are diverse, and while all share certain characteristics, they can vary significantly in many ways. Learn about how Type I, II and III systems compare in their distribution, complex composition, and their processes for surveillance and targeting, prevention of autoimmunity, and interference.
CRISPR has become well-known as a gene editing tool, and most people who have heard of CRISPR are likely unaware of its role as a prokaryotic immune system. But even as the number of CRISPR based molecular biology tools continue to rise, the ability of researchers to create these tools rests on the basic biology research that has revealed details about those immune systems. These discoveries are ongoing – while the understanding of CRISPR biology has greatly expanded in recent years, there are many details that remain unclear in even the most well-studied systems, and new subtypes and variant systems are still being discovered. Check out below to learn about how the basic biology characteristics of Type I and Type III systems - are being used to create tools.
CRISPR systems are widespread throughout bacteria and archaea, and they are also diverse. The three best-characterized types of systems are Types I, II and III. Here are some key areas of similarity and contrast between the three system types.
Read MoreType II systems, also known as CRISPR-Cas9 systems, are widely-known because of their use as genetic engineering tools. Type II systems identify and cleave double-stranded DNA from phages. Learn more in our Type II Interference page.
Read MoreCRISPR-Cas9 gene editing tools took off rapidly because of their simplicity, flexibility and precision, characteristics that are rooted in the basic biology of the Type II CRISPR systems. Learn more on our Type II Tools page.
Read MoreType I systems are the most wide-spread CRISPR systems in nature. Like the more-well known Type II systems, Type I systems identify and cleave double-stranded DNA from phages, but they use a multi-subunit CRISPR complex to do so. Read more to learn how Type I interference works.
Read MoreType III CRISPR systems use a multi-subunit complex and are unique in that they only cleave phage DNA that is actively being transcribed. Type III interference is complex and allows for different outcomes depending on the conditions of an infection, including potentially triggering cell dormancy or death. Read more to learn how Type III interference works.
Read MoreType I systems are the most abundant CRISPR systems and were the first to be studied. While the Type II CRISPR-Cas9 systems have been popular for tool development, some researchers are taking advantage of certain features of Type I system basic biology to develop molecular biology tools. Learn more on our Type I Tools page.
Read MoreType III systems are unique in that they cleave both RNA and DNA in a transcription-dependent manner, and some tools taking advantage of their basic biology and distribution have been created. Learn more on our Type III Tools page.
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