{"id":19804,"date":"2018-09-20T09:32:10","date_gmt":"2018-09-20T16:32:10","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=19804"},"modified":"2018-10-01T09:36:18","modified_gmt":"2018-10-01T16:36:18","slug":"decoding-the-structure-of-an-rna-based-crispr-system","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/decoding-the-structure-of-an-rna-based-crispr-system\/","title":{"rendered":"Decoding the structure of an RNA-based CRISPR system"},"content":{"rendered":"

LA JOLLA\u2014Over the past several years, CRISPR-Cas9 has moved beyond the lab bench and into the public zeitgeist. This gene-editing tool holds promise for correcting defects inside individual cells and potentially healing or preventing many human ailments. But the Cas9 system alters DNA, not RNA, and some experts believe that being able to modify RNA ultimately may prove just as useful.<\/p>\n

Now scientists from the Salk Institute are reporting for the first time the detailed molecular structure of CRISPR-Cas13d, a promising enzyme for emerging RNA-editing technology. They were able to visualize the enzyme thanks to cryo-electron microscopy (cryo-EM), a cutting-edge technology that enables researchers to capture the structure of complex molecules in unprecedented detail. The findings were reported September 20, 2018, in the journal Cell<\/em><\/a>.<\/p>\n

\"\"
From left: Silvana Konermann, Cheng Zhang, Dmitry Lyumkis and Patrick Hsu<\/p>\n

Click here<\/a> for a high-resolution image<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cThis paper provides a molecular blueprint for RNA-targeted genetic engineering,\u201d says Salk Assistant Professor Dmitry Lyumkis<\/a>, a structural biologist and one of the corresponding authors of the study. \u201cIt adds to the breadth of tools that are needed for conducting this kind of crucial biomedical research.\u201d<\/p>\n

Derived from genes originally found in bacteria, CRISPR has been described as \u201cmolecular scissors\u201d or a \u201cword processing program for living cells.\u201d It swaps out one segment of genetic code with another. In the CRISPR-Cas9 system, Cas9 is the enzyme that cuts DNA. Having editing tools for RNA, however, would allow scientists to modify a gene\u2019s activity without making a permanent\u2014and potentially dangerous\u2014change to the gene itself.<\/p>\n

\u201cDNA is constant, but what\u2019s always changing are the RNA messages that are copied from the DNA,\u201d says Salk Research Associate Silvana Konermann, a Howard Hughes Medical Institute Hanna Gray Fellow and one of the study\u2019s first authors. \u201cBeing able to modulate those messages by directly controlling the RNA has important implications for influencing a cell\u2019s fate.\u201d<\/p>\n

Earlier this year, Konermann and Helmsley-Salk Fellow Patrick Hsu<\/a> published another paper in Cell<\/a> <\/em>discovering the family of enzymes called CRISPR-Cas13d and reporting that this alternate CRISPR system was effective in recognizing and cutting RNA. The team also showed this tool could be used to correct a disease-causing protein imbalance in cells from a person with dementia.<\/p>\n

The new study, a collaboration between the Lyumkis and Hsu labs, built on the discovery of the Cas13d family and provides the molecular details that explain how it works.<\/p>\n

\u201cIn our previous paper, we discovered a new CRISPR family that can be used to engineer RNA directly inside of human cells,\u201d says Hsu, who is the other corresponding author of the new work. \u201cNow that we\u2019ve been able to visualize the structure of Cas13d, we can see in more detail how the enzyme is guided to the RNA and how it is able to cut the RNA. These insights are allowing us to improve the system and make the process more effective, paving the way for new strategies to treat RNA-based diseases.\u201d<\/p>\n

The team used cryo-EM to reveal new details into Cas13d by freezing the enzyme in different, dynamic states, allowing researchers to decode a range of activities instead of just seeing one activity at a single point in time.<\/p>\n

\u201cThis enabled us to see how Cas13d guides, binds and targets the RNA,\u201d says Cheng Zhang, a research associate in the Lyumkis lab and the paper\u2019s other first author. \u201cWe hope this new knowledge will help expand on the power of gene-editing tools.\u201d<\/p>\n

The paper\u2019s other authors were Nicholas J. Brideau and Peter Lotfy of Salk; Xuebing Wu of the Whitehead Institute for Biomedical Research; and Scott J. Novick, Timothy Strutzenberg and Patrick R. Griffin of The Scripps Research Institute.<\/p>\n

This work was supported by a Howard Hughes Medical Institute Hannah H. Gray Fellowship; a Helen Hay Whitney Foundation Fellowship; National Institutes of Health grants NIH-NCI CCSG P30 014195, DP5 OD021369, DP5 OD021396 and U54GM103368; and the Helmsley Charitable Trust.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[320],"disease-research":[122],"class_list":["post-19804","disclosure","type-disclosure","status-publish","hentry","faculty-dmitry-lyumkis","disease-research-immune-system-biology"],"acf":[],"yoast_head":"\nDecoding the structure of an RNA-based CRISPR system - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/decoding-the-structure-of-an-rna-based-crispr-system\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Decoding the structure of an RNA-based CRISPR system - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Over the past several years, CRISPR-Cas9 has moved beyond the lab bench and into the public zeitgeist. 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