2026-09-17 カリフォルニア大学バークレー校（UCB）
Kenneth Loi shows how VIPR RNA (in pink) snakes around the double helix of DNA (yellow and green) to form a unique triplex structure. (Photo: Glenn Ramit)
＜関連情報＞
- https://innovativegenomics.org/news/vipr-systems-origins-of-crispr/
- https://www.science.org/doi/10.1126/science.aei0498
- https://www.science.org/doi/10.1126/science.aei3472
- https://www.science.org/doi/10.1126/science.ael0758
- https://www.science.org/doi/10.1126/science.adq0553
CRISPR-Casの起源におけるRNA誘導型DNA認識のための非連続コード A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas
Peter H. Yoon, Kenneth J. Loi, Zeyuan Terry Zhang, Trevor A. Docter, […] , and Jennifer A. Doudna
Science Published:17 Sep 2026
DOI:https://doi.org/10.1126/science.aei0498
Abstract
CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors and VIPR RNAs (vrRNAs) comprising alternating GGY/NN motifs. Unlike canonical guide RNAs that pair with target nucleic acids through contiguous complementarity, vrRNAs recognize double-stranded DNA through a noncontiguous code in which the variable NN dinucleotides collectively specify a gapped target sequence. Natural vrRNA targets suggest that VIPR systems act against competing phages, and we demonstrate programmable phage defense by redirecting the complex for transcriptional repression. These results suggest that adaptive immunity originated from ancient warfare between viruses, revealing a previously unidentified logic for encoding information in sequence.
VIPR RNA誘導型DNA認識による非連続幾何学的三重らせん形成 VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation
Peter H. Yoon Trevor A. Docter, Zeyuan Terry Zhang, Kenneth Loi, […] , and Jennifer A. Doudna
Science Published:17 Sep 2026
DOI:https://doi.org/10.1126/science.aei3472
Abstract
Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo–electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.
RNA誘導免疫のウイルス起源 古代のウイルス戦争が、現代のクラス1 CRISPR細菌防御システムの根源にある可能性がある A viral origin for RNA-guided immunity Ancient viral warfare could be at the root of modern class 1 CRISPR bacterial defense systems
Jack P. K. Bravo
Science Published:17 Sep 2026
DOI:https://doi.org/10.1126/science.ael0758
Abstract
Bacteria use clustered regularly interspaced short palindromic repeats (CRISPR)–Cas systems as defense against viruses. After infection, CRISPR systems capture pieces of invading nucleic acids and insert them into the bacterial genome. These sequences provide genetic memory of previous infections and are later copied into guide RNAs that direct Cas enzymes to matching viral nucleic acids. Class 2 CRISPR systems rely on a single Cas enzyme, whereas class 1 systems use multiprotein assemblies. The origins of class 2 systems are well understood (1, 2), but those of class 1 systems have remained elusive. On pages 1230 and 1236 of this issue, Yoon et al. (3) and Yoon et al. (4), respectively, report the identification of viral interference programmable repeat (VIPR) systems, which are a plausible origin for multiunit CRISPR effectors. Understanding how RNA-guided immunity emerged could expand the arsenal of programmable tools for precise genetic manipulation.
構造に基づいた祖先型CRISPR-Cas13リボヌクレアーゼの発見 Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases
Peter H. Yoon, Zeyuan Zhang, Kenneth J. Loi, Benjamin A. Adler, […] , and Jennifer A. Doudna
Science Published:18 Jul 2024
DOI:https://doi.org/10.1126/science.adq0553
Abstract
The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an) and further trace Cas13 origins to defense-associated ribonucleases. Despite being one-third the size of other Cas13s, Cas13an mediates robust programmable RNA depletion and defense against diverse bacteriophages. However, unlike its larger counterparts, Cas13an uses a single active site for both CRISPR RNA processing and RNA-guided cleavage, revealing that the ancestral nuclease domain has two modes of activity. Discovery of Cas13an deepens our understanding of CRISPR-Cas evolution and expands opportunities for precision RNA editing, showcasing the promise of structure-guided genome mining.
