Annotation and evaluation of base editing outcomes in multiple cell types using CRISPRbase.

CRISPR-Cas base editing (BE) system is a powerful tool to expand the scope and efficiency of genome editing with single-nucleotide resolution. The editing efficiency, product purity, and off-target effect differ among various BE systems. Herein, we developed CRISPRbase (http://crisprbase.maolab.org), by integrating 1 252 935 records of base editing outcomes in more than 50 cell types from 17 species. CRISPRbase helps to evaluate the putative editing precision of different BE systems by integrating multiple annotations, functional predictions and a blasting system for single-guide RNA sequences. We systematically assessed the editing window, editing efficiency and product purity of various BE systems. Intensive efforts were focused on increasing the editing efficiency and product purity of base editors since the byproduct could be detrimental in certain applications. Remarkably, more than half of cancer-related off-target mutations were non-synonymous and extremely damaging to protein functions in most common tumor types. Luckily, most of these cancer-related mutations were passenger mutations (4840/5703, 84.87%) rather than cancer driver mutations (863/5703, 15.13%), indicating a weak effect of off-target mutations on carcinogenesis. In summary, CRISPRbase is a powerful and convenient tool to study the outcomes of different base editors and help researchers choose appropriate BE designs for functional studies.

The Roles of Gibberellins in Regulating Leaf Development.

Plant growth and development are correlated with many aspects, including phytohormones, which have specific functions. However, the mechanism underlying the process has not been well elucidated. Gibberellins (GAs) play fundamental roles in almost every aspect of plant growth and development, including cell elongation, leaf expansion, leaf senescence, seed germination, and leafy head formation. The central genes involved in GA biosynthesis include GA20 oxidase genes (GA20oxs), GA3oxs, and GA2oxs, which correlate with bioactive GAs. The GA content and GA biosynthesis genes are affected by light, carbon availability, stresses, phytohormone crosstalk, and transcription factors (TFs) as well. However, GA is the main hormone associated with BR, ABA, SA, JA, cytokinin, and auxin, regulating a wide range of growth and developmental processes. DELLA proteins act as plant growth suppressors by inhibiting the elongation and proliferation of cells. GAs induce DELLA repressor protein degradation during the GA biosynthesis process to control several critical developmental processes by interacting with F-box, PIFS, ROS, SCLl3, and other proteins. Bioactive GA levels are inversely related to DELLA proteins, and a lack of DELLA function consequently activates GA responses. In this review, we summarized the diverse roles of GAs in plant development stages, with a focus on GA biosynthesis and signal transduction, to develop new insight and an understanding of the mechanisms underlying plant development.