Chloroplastic RNA structurome for RNA-targeted herbicide discovery

Overview

Weed resistance to existing herbicides is a growing agricultural challenge, creating urgent demand for chemicals with new modes of action. This project proposes a novel strategy: targeting RNA structures within chloroplast transcripts with small molecule herbicides. By mapping the chloroplastic RNA structurome, the research aims to identify conserved and structurally stable RNA motifs found in essential plant genes. These motifs represent promising, largely untapped targets for RNA-targeted herbicide development, offering a new frontier to overcome current resistance issues.

Technical specifications

Research approach:

• In vivo chemical probing of RNA in temperature-treated plant samples or isolated chloroplasts to covalently modify unstructured nucleotides
• Bioinformatic calculation of structural stability and conservation across the chloroplastic transcriptome
• Identification of highly stable, conserved chloroplastic RNA structures as candidate druggable targets
• Use of identified structures as seeds to find related motifs in other species
• Selection of chloroplastic-specific, highly stable structures as potential herbicide targets

Scientific basis:

• Regulatory RNA structures are typically found in transcripts critical for cellular activity
• Conserved structures often appear in multiple related transcripts, enabling coordinated regulation
• Targeting a single structure shared across multiple chloroplastic transcripts can produce potent herbicide effects
• Applies high-throughput in vitro RNA-drug binding screening methods from pharmaceutical drug discovery to herbicide development

Technology readiness level

This project is at an early research stage, focused on hypothesis validation and target identification. The proposed methods leverage established techniques in RNA biology, including in vivo RNA structure determination and bioinformatic analysis of structural conservation. The next steps involve experimental determination of the chloroplastic RNA structurome, computational identification of conserved and stable motifs, and prioritization of candidate targets for subsequent small molecule screening and herbicide development.