Subgenomic messenger RNAs: Mastering regulation of (+)-strand RNA virus life cycle

Sztuba-Solińska, Joanna; Stollar, Victor; Bujarski, Józef J.

doi:10.1016/j.virol.2011.02.007

Cited by 80 publications

(64 citation statements)

References 126 publications

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“…The presence of CCS at the 5′ ends of PEMV2 gRNA and sgRNA is similar to what is found for related carmoviruses (Guan et al , 2000). CCS-complementary sequences are likely promoters for the RdRp, and could be used to generate sgRNA either following premature termination of minus-strand synthesis or by internal initiation of transcription using the minus-strand gRNA as template (Sztuba-Solinska et al , 2011). sgRNA2 of TCV (encoding the CP) is synthesized following premature termination of minus-strand synthesis, with the CCS just downstream (in the plus-strand) from a stable hairpin (Wang and Simon, 1997; Wu et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

Differential use of 3’CITEs by the subgenomic RNA of Pea enation mosaic virus 2

Gao

Simon

2017

Virology

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The genomic RNA (gRNA) of Pea enation mosaic virus 2 (PEMV2) is the template for p33 and −1 frameshift product p94. The PEMV2 subgenomic RNA (sgRNA) encodes two overlapping ORFs, p26 and p27, which are required for movement and stability of the gRNA. Efficient translation of p33 requires two of three 3′ proximal cap-independent translation enhancers (3′CITEs): the kl-TSS, which binds ribosomes and engages in a long-distance interaction with the 5’end; and the adjacent eIF4E-binding PTE. Unlike the gRNA, all three 3′CITEs were required for efficient translation of the sgRNA, which included the ribosome-binding 3′TSS. A hairpin in the 5′ proximal coding region of p26/p27 supported translation by the 3′CITEs by engaging in a long-distance RNA:RNA interaction with the kl-TSS. These results strongly suggest that the 5′ ends of PEMV2 gRNA and sgRNA connect with the 3′UTR through similar long-distance interactions while having different requirements for 3′CITEs.

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Section: Discussionmentioning

confidence: 99%

Differential use of 3’CITEs by the subgenomic RNA of Pea enation mosaic virus 2

Gao

Simon

2017

Virology

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“…Delayed structural protein synthesis and transcription of large amounts of sgRNA is a common theme in positive-sense RNA viruses and has been suggested to be a mechanism to overcome host translational repression, and possibly to promote packaging into virions of the newly synthesized viral genomes through inhibiting their translation [ 66 ] . The genome of HAstV contains highly conserved 5 ¢ and 3 ¢ UTRs [ 48 ] .…”

Section: Transcription/replicationmentioning

confidence: 99%

Replication Cycle of Astroviruses

Méndez

Murillo

Velázquez

et al. 2012

Astrovirus Research

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Astrovirus infections cause gastroenteritis in mammals and have been identi fi ed as causative agents of diverse pathologies in birds such as hepatitis in ducks and poult enteritis mortality syndrome (PEMS), which causes enteritis and thymic and bursal atrophy in turkeys. Human astroviruses are recognized as the second leading cause of childhood viral gastroenteritis worldwide. Eight traditional astrovirus serotypes have been identi fi ed in humans, but recently novel astrovirus strains isolated from humans have been associated with diseases other than gastroenteritis. Herein we summarize our current knowledge of the astrovirus life cycle. Though there are gaps in our understanding of astrovirus replication, similarities can be drawn from Picornaviridae and Caliciviridae virus families. There are, however, unique characteristics of the astrovirus life cycle, including intracellular proteolytic processing of viral particles by cellular caspases, which has been shown to be required for the maturation and exit of viral progeny.

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“…The MNV sgRNA also encodes the VF1 protein, an antagonist of the innate immune response (12). Production of an sgRNA during the viral life cycle is a common feature of many positive-sense RNA viruses (14), and it is often used to control the expression of the viral proteins.…”

mentioning

confidence: 99%

The Murine Norovirus Core Subgenomic RNA Promoter Consists of a Stable Stem-Loop That Can Direct Accurate Initiation of RNA Synthesis

Yunus

Lin

Bailey

et al. 2015

J Virol

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All members of the Caliciviridae family of viruses produce a subgenomic RNA during infection. The subgenomic RNA typically encodes only the major and minor capsid proteins, but in murine norovirus (MNV), the subgenomic RNA also encodes the VF1 protein, which functions to suppress host innate immune responses. To date, the mechanism of norovirus subgenomic RNA synthesis has not been characterized. We have previously described the presence of an evolutionarily conserved RNA stem-loop structure on the negative-sense RNA, the complementary sequence of which codes for the viral RNA-dependent RNA polymerase (NS7). The conserved stem-loop is positioned 6 nucleotides 3= of the start site of the subgenomic RNA in all caliciviruses. We demonstrate that the conserved stem-loop is essential for MNV viability. Mutant MNV RNAs with substitutions in the stem-loop replicated poorly until they accumulated mutations that revert to restore the stem-loop sequence and/or structure. The stem-loop sequence functions in a noncoding context, as it was possible to restore the replication of an MNV mutant by introducing an additional copy of the stem-loop between the NS7-and VP1-coding regions. Finally, in vitro biochemical data suggest that the stem-loop sequence is sufficient for the initiation of viral RNA synthesis by the recombinant MNV RNA-dependent RNA polymerase, confirming that the stem-loop forms the core of the norovirus subgenomic promoter. IMPORTANCENoroviruses are a significant cause of viral gastroenteritis, and it is important to understand the mechanism of norovirus RNA synthesis. Here we describe the identification of an RNA stem-loop structure that functions as the core of the norovirus subgenomic RNA promoter in cells and in vitro. This work provides new insights into the molecular mechanisms of norovirus RNA synthesis and the sequences that determine the recognition of viral RNA by the RNA-dependent RNA polymerase. N oroviruses, members of the Caliciviridae family of small positive-sense RNA viruses, are a major cause of viral gastroenteritis in the developed world (1, 2). Despite their impact, noroviruses remain poorly characterized, as an in-depth understanding of the molecular mechanisms of norovirus genome translation and replication has been hampered by the inability to culture human norovirus (3). Murine norovirus (MNV) is a model system with which to understand the norovirus life cycle (4), as it replicates in cultured cells (5) and a number of tractable reverse genetics systems are available (6-9). Studies of MNV have therefore led to a number of significant advances in the understanding of the molecular mechanism of norovirus genome translation and replication (reviewed in reference 10).The norovirus RNA genome typically carries three open reading frames (ORFs) (11). MNV also has an additional ORF in the region overlapping the VP1-coding region (12, 13) (Fig. 1A). All members of the Caliciviridae family of small positive-sense RNA viruses synthesize a shorter-than-genome-length, subgenomic RNA (sgRNA)...

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Subgenomic messenger RNAs: Mastering regulation of (+)-strand RNA virus life cycle

Cited by 80 publications

References 126 publications

Differential use of 3’CITEs by the subgenomic RNA of Pea enation mosaic virus 2

Differential use of 3’CITEs by the subgenomic RNA of Pea enation mosaic virus 2

Replication Cycle of Astroviruses

The Murine Norovirus Core Subgenomic RNA Promoter Consists of a Stable Stem-Loop That Can Direct Accurate Initiation of RNA Synthesis

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