Translational Regulation in the 5′UTR of Enteroviruses
type: CreativeWork
description: The genus Enterovirus consists of a large group of positive-sense RNA viruses, with over 100 serotypes known to be human pathogens. Disease phenotype in humans ranges from sub- clinical to acute flaccid paralysis and treatment options for infection with these viruses are limited, with only few antivirals and vaccienes available. Recent work has shown that many enteroviruses encode their proteins within two open reading frames (ORFs), the polyprotein ORF (ppORF) and the upstream ORF (uORF). The uORF encodes a small protein, UP. In addition to the canonical uORF start codon (uAUG), situated on the domain six (dVI) stem loop structure within the viral internal ribosome entry site (IRES), some viruses have additional AUGs both up and downstream of this structure. However, whether these represent alternative sites of translation initiation has not yet been determined. Since many enteroviruses have additional AUGs in the region of the dVI AUG, we evaluated its effects on translation in three frames in coxsackievirus A13 (CVA-13). CVA-13 naturally has an additional AUG (uuAUG) 10 nucleotides upstream of the dVI AUG (uAUG), where UP is encoded. Analysis of the translational landscape of infected cells, through profiling of initiating ribosomes, demonstrated that both the uAUG and uuAUG codons can be used as sites of translation initiation. Using luciferase reporters, we determined the efficiency of Enterovirus alphacoxsackie and coxsackiepol IRES-mediated translation in three frames, further confirming that alternative initiation sites exist in natural isolates and that both upstream AUGs can be utilised for translation initiation. In some cases, UP translation initiates at the uuAUG rather than the canonical uAUG. Thus, uAUG-proximal start codons must also be considered when defining the coding capacity of enteroviruses. Although alternative start codons within enteroviruses provide additional sites for translation initiation, in CVA-13, the presence of the uuAUG is not ne…
abstract: The genus Enterovirus consists of a large group of positive-sense RNA viruses, with over 100 serotypes known to be human pathogens. Disease phenotype in humans ranges from sub- clinical to acute flaccid paralysis and treatment options for infection with these viruses are limited, with only few antivirals and vaccienes available. Recent work has shown that many enteroviruses encode their proteins within two open reading frames (ORFs), the polyprotein ORF (ppORF) and the upstream ORF (uORF). The uORF encodes a small protein, UP. In addition to the canonical uORF start codon (uAUG), situated on the domain six (dVI) stem loop structure within the viral internal ribosome entry site (IRES), some viruses have additional AUGs both up and downstream of this structure. However, whether these represent alternative sites of translation initiation has not yet been determined. Since many enteroviruses have additional AUGs in the region of the dVI AUG, we evaluated its effects on translation in three frames in coxsackievirus A13 (CVA-13). CVA-13 naturally has an additional AUG (uuAUG) 10 nucleotides upstream of the dVI AUG (uAUG), where UP is encoded. Analysis of the translational landscape of infected cells, through profiling of initiating ribosomes, demonstrated that both the uAUG and uuAUG codons can be used as sites of translation initiation. Using luciferase reporters, we determined the efficiency of Enterovirus alphacoxsackie and coxsackiepol IRES-mediated translation in three frames, further confirming that alternative initiation sites exist in natural isolates and that both upstream AUGs can be utilised for translation initiation. In some cases, UP translation initiates at the uuAUG rather than the canonical uAUG. Thus, uAUG-proximal start codons must also be considered when defining the coding capacity of enteroviruses. Although alternative start codons within enteroviruses provide additional sites for translation initiation, in CVA-13, the presence of the uuAUG is not ne…
author: O'Connor, Rhian
language: eng
keywords: Enterovirus, Translation initiation, uORF, Intestinal organoids
license: https://www.repository.cam.ac.uk/bitstreams/f26cd937-142f-4b9d-bcc5-02d4118d57f4/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-09-30
date modified: 2026-07-24T01:33:05Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.117818