Quantification and transcriptome profiling reveal abundant, dynamic and translatable dephospho-CoA-capped RNAs.

Hu, Hao; Zhang, Qiyue; Ma, Xuan; Chu, Hsu-Feng; Wang, Han; Guo, Yiwen; Bai, Yuze; Wang, Qianyu et al. · Nat Biotechnol · 2026

basic_science · Level V

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Abstract

Cellular metabolites have emerged as noncanonical RNA caps. Despite its early discovery as an RNA cap, the dephospho-CoA (dpCoA) cap remains largely uncharacterized because of a lack of detection technologies. Here we use biochemical and structural analysis to identify Arabidopsis NUDT11 as a specific decapping enzyme toward dpCoA-RNA. Leveraging this specificity, we develop biochemical and transcriptomic methods to quantify and profile dpCoA-RNA across the genome, revealing that dpCoA-RNAs exist across species and exhibit tissue-specific and/or condition-specific variations. In Arabidopsis, dpCoA-RNAs possess distinct transcription start sites and respond more rapidly to high light intensity as compared to 7-methylguanosine (m<sup>7</sup>G)-capped RNAs. Moreover, Arabidopsis dpCoA-RNAs can reach up to 15% of m<sup>7</sup>G-capped RNAs in abundance and are associated with translating ribosomes. We further demonstrate that an in vitro transcribed dpCoA-RNA is translated in human cells. This study uncovers a dynamic dpCoA cap that may potentially influence gene expression and establishes a toolkit for future investigations.