CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

Genome Biology

Martin Crespi¹  Jeremie Bazin¹  Stefan T. Arold²  Afaque A. Momin²  Haroon Butt³  Ayman Eid³  Magdy M. Mahfouz³ 

[1] CNRS, INRA, Institute of Plant Sciences Paris-Saclay IPS2, Univ Paris Sud, Univ Evry, Univ Paris-Diderot, Sorbonne Paris-Cite, Universite Paris-Saclay;Division of Biological and Environmental Sciences and Engineering, Computational Bioscience Research Center, KAUST;Laboratory for Genome Engineering and Synthetic Biology, King Abdullah University of Science and Technology (KAUST);

关键词: Directed evolution;    Genome engineering;    Spliceosome;    SF3B complex;    SF3B1;    Splicing modulators;   

DOI  :  10.1186/s13059-019-1680-9

来源: DOAJ

【 摘 要 】

Abstract Increasing genetic diversity via directed evolution holds great promise to accelerate trait development and crop improvement. We developed a CRISPR/Cas-based directed evolution platform in plants to evolve the rice (Oryza sativa) SF3B1 spliceosomal protein for resistance to splicing inhibitors. SF3B1 mutant variants, termed SF3B1-GEX1A-Resistant (SGR), confer variable levels of resistance to splicing inhibitors. Studies of the structural basis of the splicing inhibitor binding to SGRs corroborate the resistance phenotype. This directed evolution platform can be used to interrogate and evolve the molecular functions of key biomolecules and to engineer crop traits for improved performance and adaptation under climate change conditions.

【 授权许可】

Unknown