Functional viromic screens uncover regulatory RNA elements

The number of sequenced viral genomes has surged recently, presenting an opportunity to understand viral diversity and uncover unknown regulatory mechanisms. Here, we conducted a screening of 30,367 viral segments from 143 species representing 96 genera and 37 families. Using a library of viral segments in 30 UTR, we identified hundreds of elements impacting RNA abundance, translation, and nucleocytoplasmic distribution. To illustrate the power of this approach, we investigated K5, an element conserved in kobuviruses, and found its potent ability to enhance mRNA stability and translation in various contexts, including adeno-associated viral vectors and synthetic mRNAs. Moreover, we identified a previously uncharacterized protein, ZCCHC2, as a critical host factor for K5. ZCCHC2 recruits the terminal nucleotidyl transferase TENT4 to elongate poly(A) tails with mixed sequences, delaying deadenylation. This study provides a unique resource for virus and RNA research and highlights the potential of the virosphere for biological discoveries.

Automated summary

Recent advancements in the sequencing of viral genomes have allowed for a better understanding of viral diversity and unknown regulatory mechanisms. In this study, researchers screened 30,367 viral segments from 143 species and identified hundreds of elements impacting RNA abundance, translation, and distribution. By investigating a conserved element called K5, they discovered its ability to enhance mRNA stability and translation. Additionally, they identified a previously unknown protein, ZCCHC2, as a critical host factor for K5. This study provides valuable information for virus and RNA research and highlights the potential of the virosphere for biological discoveries.