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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Harnessing CRISPR-Cas adaptation for RNA recording and beyond

  • Gyeong-Seok Oh (Center for RNA Research, Institute for Basic Science) ;
  • Seongjin An (Center for RNA Research, Institute for Basic Science) ;
  • Sungchul Kim (Center for RNA Research, Institute for Basic Science)
  • Received : 2023.04.03
  • Accepted : 2023.04.04
  • Published : 2024.01.31
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Abstract

Prokaryotes encode clustered regularly interspaced short palindromic repeat (CRISPR) arrays and CRISPR-associated (Cas) genes as an adaptive immune machinery. CRISPR-Cas systems effectively protect hosts from the invasion of foreign enemies, such as bacteriophages and plasmids. During a process called 'adaptation', non-self-nucleic acid fragments are acquired as spacers between repeats in the host CRISPR array, to establish immunological memory. The highly conserved Cas1-Cas2 complexes function as molecular recorders to integrate spacers in a time course manner, which can subsequently be expressed as crRNAs complexed with Cas effector proteins for the RNA-guided interference pathways. In some of the RNA-targeting type III systems, Cas1 proteins are fused with reverse transcriptase (RT), indicating that RT-Cas1-Cas2 complexes can acquire RNA transcripts for spacer acquisition. In this review, we summarize current studies that focus on the molecular structure and function of the RT-fused Cas1-Cas2 integrase, and its potential applications as a directional RNA-recording tool in cells. Furthermore, we highlight outstanding questions for RT-Cas1-Cas2 studies and future directions for RNA-recording CRISPR technologies.

Keywords

Acknowledgement

This work was supported by IBS-R008-D1, Young Scientist Fellowship program of the Institute for Basic Science from the Ministry of Science and ICT of Korea.

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