Auxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFB functionality, as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin 1 to 4 (RN1 to -4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical, and morphological levels. This selective activity is explained by their ability to consistently promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, we performed a genetic screen using RN4, the RN with the greatest potential for dissecting auxin perception, which revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions, as well as offering opportunities to discover new molecular players involved in auxin responses.

Center for Plant Systems Biology Vlaams Instituut voor Biotechnologie 9052 Ghent Belgium

Centre for Plant Sciences University of Leeds LS2 9JT Leeds United Kingdom

Department of Forest Genetics and Plant Physiology Umeå Plant Science Centre Swedish University of Agricultural Sciences SE 901 83 Umeå Sweden

Department of Forest Genetics and Plant Physiology Umeå Plant Science Centre Swedish University of Agricultural Sciences SE 901 83 Umeå Sweden;

Department of Molecular and Cellular Biology University of California Davis CA 95616

Department of Plant Biology Swedish University of Agricultural Sciences The Linnean Centre for Plant Biology in Uppsala SE 75007 Uppsala Sweden

Department of Plant Biotechnology and Bioinformatics Ghent University 9052 Ghent Belgium

Institute of Physical and Theoretical Chemistry University of Bonn 53121 Bonn Germany

Laboratories for Chemical Biology Umeå Chemical Biology Consortium Sweden Department of Chemistry Umeå University SE 901 87 Umeå Sweden

Laboratory of Growth Regulators Faculty of Science Palacký University CZ 78371 Olomouc Czech Republic

Laboratory of Growth Regulators Institute of Experimental Botany The Czech Academy of Sciences CZ 78371 Olomouc Czech Republic

Section of Cell and Developmental Biology University of California San Diego La Jolla CA 92093 0116

Sup'Biotech IONIS Education Group 94800 Villejuif France

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