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Functional viromic screens uncover regulatory RNA elements

ABSTRACT: 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 3′ 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.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jenny Seo

LAB HEAD: V. Narry Kim

PROVIDER: PXD041296 | Pride | 2023-06-23

REPOSITORIES: Pride

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			Action	DRS
	H_Sapiens_Sprot_20221011.fasta	Fasta
	RaPID_B_NAQ448_J100_230316_1.mzML	Mzml
	RaPID_B_NAQ448_J100_230316_1.raw	Raw
	RaPID_B_NAQ448_J100_230316_2.mzML	Mzml
	RaPID_B_NAQ448_J100_230316_2.raw	Raw

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