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UniProt release 2019_01

Published January 16, 2019

Headline

Engaging and disengaging: CRISPR rings

CRISPR-Cas systems are an RNA-guided adaptive immune response that bacteria and archaea use to defend against invasive genetic elements of bacterial (plasmid) or viral origin. Pieces of foreign DNA incorporated into CRISPR arrays provide a “memory” of having encountered the invader. These arrays are transcribed and processed, and the resulting CRISPR RNA (crRNA) is used by the interference complex to recognize the invader if it is re-encountered. Once recognized, foreign nucleic acids are quickly degraded, providing immunity. There are different types of CRISPR-Cas systems, mainly characterized by the presence or absence of certain Cas proteins. For example, the Cas3, Cas9, and Cas10 proteins are hallmarks of the CRISPR/Cas types I, II and III, respectively. The best known system is the type II Cas9-encoding system, which has been coopted by scientists for genome editing. The most intriguing one is the type III system, which has additional, novel control mechanisms not found in the other systems.

The type III interference complex is composed of crRNA, Cas10 and proteins Csm2, Csm3, Csm4 and Csm5. Once the target RNA has bound to the Csm interference complex it is cleaved by the complex, which acts as a sequence-specific endoribonuclease (RNase). There is an additional component to this system: Csm6. Under basal conditions, Csm6 is an inactive RNase and is not part of the Csm complex, however its presence is required for full CRISPR-Cas immunity where it non-specifically degrades invader-derived RNA transcripts. How then is Csm6 RNase activity turned on and, once activated, how is it turned off, considering that an uncontrolled RNase activity could be detrimental to the cell? The answer to these questions has been revealed in recent publications. Homodimeric Csm6 is activated by cyclic oligoadenylates (cOA), ring-shaped second messengers synthesized by the C-terminal GGDEF (also called Palm) domain of Cas10. Binding of cOA to the Csm6 dimer interface pocket formed by its CARF (CRISPR-associated Rossman fold) domains allosterically regulates its RNase activity. The type of cyclic oligoadenylates produced is species-specific. Streptococcus thermophilus and Enterococcus italicus make cyclic hexaadenylate (cA6), while Csm6 of Thermus thermophilus is stimulated by cyclic tetraadenylate (cA4), suggesting Cas10 in this organism synthesizes cA4. As the target RNA associated with the CRISPR complex is degraded, the cOA synthase activity of Cas10 shuts off, halting second messenger synthesis. Additionally, 2 proteins with ring-specific nuclease activity able to degrade cOA have been recently isolated from Saccharolobus solfataricus (formerly called Sulfolobus solfataricus), which would turn down Csm6 activity and prevent uncontrolled degradation of cellular RNA.

As of this release several Cas10 proteins and the ring nucleases of S.solfataricus have been annotated and can be retrieved.

UniProtKB news

Cross-references to jPOST

Cross-references have been added to jPOST, a proteomics database containing re-analysis results with unified criteria for raw data from several ProteomeXchange (PX) repositories.

jPOST is available at https://globe.jpostdb.org/.

The format of the explicit links is:

Resource abbreviationjPOST
Resource identifierUniProtKB accession number

Example: Q8IY92

Show all entries having a cross-reference to jPOST.

Text format

Example: Q8IY92

DR   jPOST; Q8IY92; -.

XML format

Example: Q8IY92

<dbReference type="jPOST" id="Q8IY92"/>

RDF format

Example: Q8IY92

uniprot:Q8IY92
  rdfs:seeAlso <http://purl.uniprot.org/jpost/Q8IY92> .
<http://purl.uniprot.org/jpost/Q8IY92>
  rdf:type up:Resource ;
  up:database <http://purl.uniprot.org/database/jPOST> .

Changes to the controlled vocabulary of human diseases

New diseases:

Modified diseases:

Deleted diseases

  • Limb-girdle muscular dystrophy 1A
  • Limb-girdle muscular dystrophy 1B
  • Limb-girdle muscular dystrophy 1C
  • Limb-girdle muscular dystrophy 2R

Changes to the controlled vocabulary for PTMs

New terms for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):

  • ADP-ribosylglycine
  • ADP-ribosyltyrosine

Changes in subcellular location controlled vocabulary

New subcellular locations:

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