#10809 OTR+NTR: CRISPR biology and GO:0043571 ! maintenance of CRISPR repeat elements

[Jim Hu]

GO:0043571 ! maintenance of CRISPR repeat elements is defined as:
"Any process involved in sustaining CRISPR repeat clusters, including capture of new spacer elements, expansion or contraction of clusters, propagation of the leader sequence and repeat clusters within a genome, transfer of repeat clusters and CRISPR-associated (cas) genes to new genomes, transcription of the CRISPR repeat arrays into RNA and processing, and interaction of CRISPR/cas loci with the host genome. CRISPR (clustered regularly interspaced short palindromic repeat) elements are a family of sequence elements containing multiple direct repeats of 24-48 bp with weak dyad symmetry which are separated by regularly sized nonrepetitive spacer sequences."

It's an is_a child of GO:0043570 ! maintenance of DNA repeat elements.

This term strikes me as an overly broad umbrella for all of CRISPR-cas biology. At the same time, it's missing the key activity of the CRISPR systems in host defense. The reference provided in the notes doesn't give a good overview of the biology.

PMID: 23495939 is an Annual Reviews article, which breaks CRISPR biology into three types of potential process terms:

• CRISPR adaptation (i.e., new spacer acquisition), is_a GO:0006259 ! DNA metabolic process. I don't think it should be an is_a of GO:0043570 ! maintenance of DNA repeat elements. The key step is the capture of new unique sequences within the repeat array.
• CRISPR-associ
• crRNA biogenesis, (transcription and RNA processing) is_a GO:0006396 ! RNA processing
• crRNA-guided target nucleic acid inactivation
  • crRNA-guided target DNA inactivation
  • crRNA-guided target RNA inactivation

IIRC cells that are defective in CRISPR adaptation can still use CRISPRs to defend against invaders that match existing crRNAs

An umbrella term for the overall process of CRISPR-mediated adaptive immunity could be over all of these, the closest appropriate parent would be GO:0044355 ! clearance of foreign intracellular DNA, but this should have a parent term that includes both RNA and DNA. Otherwise, it would be a child of GO:0006952 ! defense response. From the review, some CRISPR mediated host defense systems work against DNA and RNA (see above)

In addition to process terms, there should probably also be component terms:

• CRISPR-associated complex for antiviral defense is_a GO:0030529 ! ribonucleoprotein complex
  • CRISPR-associated complex for antiviral defense, Type I (Cascade)
  • CRISPR-associated complex for antiviral defense, Type II
  • CRISPR-associated complex for antiviral defense, Type III

One or more activity terms may also be needed.

[Tanya Berardini]

In absence of CRISPR expert, need to obtain this knowledge from scratch and integrate into GO. Priority? Estimate at the very least a day of work between reading, organizing structure, creating new terms and relationships.