In this week's Nature, University of California, Berkeley, researcher and CRISPR/Cas9 pioneer Jennifer Doudna and colleagues present data giving new insights into how the genome-editing technology zeroes in on its target. They found that the conformational state of the nuclease domain that cleaves target DNA strands directly controls the cutting activity. The discovery highlights a "proofreading mechanism" that serves as a final checkpoint before DNA double-strand break formation.
Also in Nature, a forensic analyst warns that the use of DNA to solve crimes is not without limitations — an issue that must be recognized when using genetic evidence in court. She highlights the need for a review of how DNA evidence is assessed and applied in the criminal justice system and the importance of understanding the potential for mistakes. "As the technology to generate these profiles continues to accelerate, so must our efforts to sift out possible mistakes," she argues.
And in Nature Medicine, a team led by Massachusetts General Hospital researchers report on the use of genome-wide association study data to identify microRNAs involved in cholesterol and triglyceride regulation. By analyzing genetic data from more than 188,000 individuals, the researchers found 69 non-coding RNAs near SNPs associated with abnormal levels of circulating lipids. Several of the miRNAs control the expression of proteins involved in cholesterol-lipoprotein trafficking, and either upregulating or suppressing these molecules led to altered hepatic expression of lipid- and metabolism-associated proteins in mice. Overall, the findings suggest that altered miRNA expression may contribute to abnormal blood lipid levels and predispose individuals to cardiometabolic disorders