Unravelling the Inner Workings of CRISPR
Viruses (blue) attack a bacterial cell (yellow) by injecting their genome. A new study shows how the bacterial immune system quickly targets the invading DNA. Credit: Lee D. Simon/SCIENCE PHOTO LIBRARY
In battles between germs, the opening shot is often an injection. A virus, intent on infecting a microbe, punctures the cell’s protective wall and inserts its own genetic code. New research from The Rockefeller University reveals how microbes act quickly to fend off the incoming threat.
The discovery, described in Nature on March 29, answers a long-standing question about the inner workings of CRISPR, a bacterial immune system that also serves as a powerful tool for editing genomes.
Scientists already knew the basics: When a bacterial cell is invaded by viral DNA, its CRISPR system captures snippets of it and catalogs those DNA pieces. Should the same virus show up again, the system will quickly recognize it.
“For about a decade, we’ve known that CRISPR works by acquiring pieces of viral DNA, but it’s been a mystery exactly when this key step in CRISPR immunity occurs during an infection,” says Luciano A. Marraffini, head of the Laboratory of Bacteriology, who studies CRISPR systems in their native bacteria.
Experiments in his lab revealed that CRISPR springs into action early on, when the virus is injecting itself into the cell.
To pinpoint the timing, the research team designed an experiment to stop the viral life cycle at different points. Joshua W. Modell, a postdoc, and Wenyan Jiang, a graduate student, then examined the CRISPR systems to see when and how they acquired spacers from the virus.
Just any DNA won’t do for CRISPR—previous research has shown it favors spacers from the loose ends of DNA. This preference narrows the options, since viral DNA takes linear form only during certain points in the infection. The rest of the time its two ends stick together, creating a circle.
The team halted the infection at three points. But regardless of when they stopped it, CRISPR continued to acquire spacers, indicating it picks them up at the beginning, around when the virus injects its genome—as a linear strand—into the cell.
An early defense
This timing matters. By taking spacers from the first part of the virus to enter the cell, CRISPR ensures it will attack the virus as soon as it shows up next time. When the researchers altered CRISPR systems to contain spacers that matched sequences at the end of the viral genome, the last part to be injected, the microbes struggled to proliferate.
“It turns out that the CRISPR system is very clever,” says Modell. “It takes advantage of a nuance of the viral infection cycle to halt an infection as early as possible.”
RNA That Helps Grow Blood Vessels Could Aid Heart Disease ResearchNews
STEEL, a noncoding RNA, acts on genes to stimulate produce of blood vessels, a finding which could advance efforts to combat heart disease.READ MORE
Brightly-Coloured Bacteria Could be Used to 'Grow' Paints and CoatingsNews
Researchers have unlocked the genetic code behind some of the brightest and most vibrant colours in nature. It is the first study of the genetics of structural colour - as seen in butterfly wings and peacock feathers - and paves the way for genetic research in a variety of structurally coloured organisms.READ MORE
1200 Year Old DNA Helps Find Living Descendants of Indigenous Taíno AmericansNews
A genomic study has found that he Taíno, a population of early indigenous Americans, have living descendants, debunking theorists who had claimed they were extinct.READ MORE
Comments | 0 ADD COMMENT
World Advanced Therapies & Regenerative Medicine Congress
May 16 - May 18, 2018