RNA-guided transcriptional repression by TIGR-Tas systems
- 1Broad Institute
Abstract
Tandem interspaced guide RNA (TIGR)-TIGR-associated protein (Tas) systems are a widespread family of RNA-guided DNA-targeting proteins whose diversity has remained uncharacterized because their arrays, unlike CRISPR arrays, lack the sequence conservation required by existing annotation tools. We developed TIGRFinder, a motif-based pipeline that identified 6,685 TIGR arrays from genomic and metagenomic data. Phylogenetic and structural analysis of Tas proteins revealed clade-specific insertions in stem-loop binding Tas proteins that co-vary with features of their cognate tigRNAs. Cryo-electron microscopy structures of two stem-loop binding TasR ribonucleoprotein complexes demonstrate how these protein insertions directly accommodate extended tigRNA stems while maintaining DNA binding through catalytically inactive RuvC domains. We also show that these catalytically dead TasR proteins, along with the nuclease-lacking TasA, function as RNA-guided transcriptional repressors. These findings establish TIGR-Tas as a functionally diverse family of RNA-guided effectors, with comprehensive annotations available through TIGRSafari (https://tigr.bio) to support further exploration and engineering.
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BibTeX
@misc{xu2026rnaguided,
title = {{RNA-guided transcriptional repression by TIGR-Tas systems}},
author = {P. Xu and L. Long and A. Zhu and S. Kim and S. Zilberzwige-Tal and N. Quinones-Olvera and L. Evegniou and D. Flam-Shepherd and R. Macrae and G. Faure and F. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750476},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750476v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - RNA-guided transcriptional repression by TIGR-Tas systems
AU - P. Xu
AU - L. Long
AU - A. Zhu
AU - S. Kim
AU - S. Zilberzwige-Tal
AU - N. Quinones-Olvera
AU - L. Evegniou
AU - D. Flam-Shepherd
AU - R. Macrae
AU - G. Faure
AU - F. Zhang
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750476
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750476v1
AB - Tandem interspaced guide RNA (TIGR)-TIGR-associated protein (Tas) systems are a widespread family of RNA-guided DNA-targeting proteins whose diversity has remained uncharacterized because their arrays, unlike CRISPR arrays, lack the sequence conservation required by existing annotation tools. We developed TIGRFinder, a motif-based pipeline that identified 6,685 TIGR arrays from genomic and metagenomic data. Phylogenetic and structural analysis of Tas proteins revealed clade-specific insertions in stem-loop binding Tas proteins that co-vary with features of their cognate tigRNAs. Cryo-electron microscopy structures of two stem-loop binding TasR ribonucleoprotein complexes demonstrate how these protein insertions directly accommodate extended tigRNA stems while maintaining DNA binding through catalytically inactive RuvC domains. We also show that these catalytically dead TasR proteins, along with the nuclease-lacking TasA, function as RNA-guided transcriptional repressors. These findings establish TIGR-Tas as a functionally diverse family of RNA-guided effectors, with comprehensive annotations available through TIGRSafari (https://tigr.bio) to support further exploration and engineering.
ER -