Why the study?
After type III CRISPR-Cas immune response, cyclic oligo-adenylate (cOA) should be cleared on time to avoid constant cellular RNA degradation.
Identifies a membrane-associated nuclease in Sulfolobus islandicus that acts as a secondary degrader of cOA in Type III CRISPR-Cas signaling.
Membrane-associated cOA degradation may limit prolonged RNA cleavage; leaves open its role and conservation in type III CRISPR termination.
Type III CRISPR-Cas systems initiate an intracellular signaling pathway to confer immunity. The signaling pathway includes synthesis of cyclic oligo-adenylate (cOA) and activation of the RNase activity of type III accessory ribonuclease Csm6/Csx1 by cOA. After the immune response, cOA should be cleared on time to avoid constant cellular RNA degradation. In this study, we find a metal-dependent cOA degradation activity in Sulfolobus islandicus. The activity is associated with the cell membrane and able to accelerate cOA clearance at a high cOA level. Further, we show that a metal-dependent and membrane-associated DHH-DHHA1 family nuclease (MAD) rapidly cleaves cOA and deactivates Csx1 ribonuclease. The cOA degradation efficiency of MAD is much higher than the cellular ring nuclease. However, the subcellular organization may prevent it from degrading nascent cOA. Together, the data suggest that MAD acts as the second cOA degrader after the ring nuclease to remove diffused redundant cOA.
No takes yet. Share an insight, caveat, or question.
Zhao et al. (2020) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: