The working dead: repurposing inactive CRISPR-associated nucleases as programmable transcriptional regulators in plants

Targeted gene manipulation is highly desirable for fundamental plant research, plant synthetic biology, and molecular breeding. The clustered regularly interspaced short palindromic repeats-associated (Cas) nuclease is a revolutionary tool for genome editing, and has received snowballing popularity for gene knockout applications in diverse organisms including plants. Recently, the nuclease-dead Cas (dCas) proteins have been repurposed as programmable transcriptional regulators through translational fusion with portable transcriptional repression or activation domains, which has paved new ways for flexible and multiplex control over the activities of target genes of interest without the need to generate DNA lesions. Here, we review the most important breakthroughs of dCas transcriptional regulators in non-plant organisms and recent accomplishments of this growing field in plants. We also provide perspectives on future development directions of dCas transcriptional regulators in plant research in hope to stimulate their quick evolution and broad applications.