CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

Haroon Butt; Ayman Eid; Afaque Ahmad Imtiyaz Momin; Jeremie Bazin; Martin Crespi; Stefan T. Arold; Magdy M. Mahfouz

doi:10.1186/s13059-019-1680-9

CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

Haroon Butt, Ayman Eid, Afaque Ahmad Imtiyaz Momin, Jeremie Bazin, Martin Crespi, Stefan T. Arold, Magdy M. Mahfouz

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60 Scopus citations

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.

Original language	English (US)
Journal	Genome biology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13059-019-1680-9
State	Published - Apr 30 2019

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10.1186/s13059-019-1680-9

https://repository.kaust.edu.sa/bitstream/10754/652834/1/s13059-019-1680-9.pdf

Cite this

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title = "CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors",

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.",

author = "Haroon Butt and Ayman Eid and Momin, {Afaque Ahmad Imtiyaz} and Jeremie Bazin and Martin Crespi and Arold, {Stefan T.} and Mahfouz, {Magdy M.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: Acknowledgements: We would like to thank members of the genome engineering and synthetic biology laboratory at KAUST for their critical discussion and technical help in this work. Funding: This work is funded by KAUST-baseline funding to Magdy Mahfouz and Stefan Arold.",

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doi = "10.1186/s13059-019-1680-9",

language = "English (US)",

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journal = "Genome Biology",

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TY - JOUR

T1 - CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

AU - Butt, Haroon

AU - Eid, Ayman

AU - Momin, Afaque Ahmad Imtiyaz

AU - Bazin, Jeremie

AU - Crespi, Martin

AU - Arold, Stefan T.

AU - Mahfouz, Magdy M.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: Acknowledgements: We would like to thank members of the genome engineering and synthetic biology laboratory at KAUST for their critical discussion and technical help in this work. Funding: This work is funded by KAUST-baseline funding to Magdy Mahfouz and Stefan Arold.

PY - 2019/4/30

Y1 - 2019/4/30

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/652834

UR - https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1680-9

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DO - 10.1186/s13059-019-1680-9

M3 - Article

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VL - 20

JO - Genome Biology

JF - Genome Biology

SN - 1465-6914

IS - 1

ER -

CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

Abstract

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