Imagine a war in which you are vastly outnumbered by an enemy that is utterly relentless attacking you is all it does. The intro to another Terminator movie? No, just another day for microbes such as bacteria and archaea, which face a never-ending onslaught from viruses and invading strands of nucleic acid known as plasmids. To survive this onslaught, microbes deploy a variety of defense mechanisms, including an adaptive-type nucleic acid-based immune system that revolves around a genetic element known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats.
Through the combination of CRISPR and squads of CRISPR-associated - "Cas" - proteins, microbes are able to utilize small customized RNA molecules to silence critical portions of an invader's genetic message and acquire immunity from similar invasions in the future. To better understand how this microbial immune system works, scientists have needed to know more about how CRISPR's customized small RNA molecules get produced. Answers have now been provided by a team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley.
In a study led by biochemist Jennifer Doudna, the research team used protein crystallography beamlines at Berkeley Lab's Advanced Light Source to produce an atomic-scale crystal structure model of an endoribonuclease called "Csy4." Doudna and her colleagues have identified Csy4 as the enzyme in prokaryotes that initiates the production of CRISPR-derived RNAs (crRNAs), the small RNA molecules that target and silence invading viruses and plasmids.
"Our model reveals that Csy4 and related endoribonucleases from the same CRISPR/Cas subfamily utilize an exquisite recognition mechanism to discriminate crRNAs from other cellular RNAs to ensure the selective production of crRNA for acquired immunity in bacteria," Doudna says. "We also found functional similarities between
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory