Paper

Arabidopsis epigenetic factor AS2 attenuates nucleolar stress by camptothecin and establishes leaf polarity by repressing a CDK inhibitor

Ando, Sayuri, Ishibashi, Nanako, Ito, Takuma, Yamazaki, Mami, Keta, Sumie, Ohbayashi, Iwai, Cha, Byung-Yoon, Sugiyama, Munetaka, Takahashi, Mari, Machida, Yasunori, Nakagawa, Ayami, Sasabe, Michiko, Ito, Masaki, Ohga, Kazuomi, Tamai, Motoki, Woo, Je-Tae, Takahashi, Hiro, Vial-Pradel, Simon, Takada, Eri, Kojima, Shoko, Iwakawa, Hidekazu, Machida, Chiyoko

2025

Overview

The Arabidopsis thaliana leaf, exhibiting a symmetrically extended flat morphology, consists of two distinct cellular domains: adaxial and abaxial layers. The ASYMMETRIC LEAVES2 (AS2) gene is essential for specifying the adaxial domain, and its protein forms nucleolar structures, termed AS2 bodies, at ribosomal-DNA loci. Numerous nucleolus-related genes have been reported to be cooperatively involved in leaf adaxialization together with AS2. However, the molecular relationships between AS2 and these genes remain unclear. To identify chemical modulators of AS2 function, we screened a chemical library containing natural products and identified eight molecules, including camptothecin, that induced filamentous leaves in the as2 mutant. Camptothecin is an inhibitor of topoisomerase I, which is required for transcription of ribosomal–RNA genes, and induces nucleolar stress. Treatment with 10-hydroxy-camptothecin increased KIP-RELATED-PROTEIN5/INHIBITOR-OF-CYCLIN-DEPENDENT-KINASE3 (KRP5/ICK3) transcript levels, encoding a CDK inhibitor, and caused notable changes in the number and morphology of AS2 bodies. Given its role in leaf morphogenesis, our findings suggest that AS2 is a key factor in establishing leaf adaxial-abaxial polarity by regulating cell proliferation and protecting against nucleolar stress through coordinated interactions with nucleolar proteins.

• Publisher: Cold Spring Harbor Laboratory
• Subject: Developmental Biology