Downregulation of Nipah Virus N mRNA Occurs through Interaction between Its 3′ Untranslated Region and hnRNP D

Hino, Kimihiro; Sato, Hiroki; Sugai, Akihiro; Katô, Masahiko; Yoneda, Misako; Kai, Chieko

doi:10.1128/jvi.02495-12

Cited by 19 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By binding to defined genomic elements and by modulating viral protein or RNA synthesis, AUF1/hnRNPD was found to accelerate or inhibit the life cycles of various RNA viruses (Paek et al 2008;Lund et al 2012;Cathcart et al 2013;Hino et al 2013;Lin et al 2014). It is quite conceivable that the methylation-enhanced RNA restructuring activity of the AUF1 p45 isoform, which was demonstrated here to support WNV replication, may underlie several of the functions of AUF1 during the replication processes of other viruses as well.…”

Section: Discussionmentioning

confidence: 67%

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45

Friedrich

Schmidt

Schierhorn

et al. 2016

RNA

View full text Add to dashboard Cite

A prerequisite for the intracellular replication process of the Flavivirus West Nile virus (WNV) is the cyclization of the viral RNA genome, which enables the viral replicase to initiate RNA synthesis. Our earlier studies indicated that the p45 isoform of the cellular AU-rich element binding protein 1 (AUF1) has an RNA chaperone activity, which supports RNA cyclization and viral RNA synthesis by destabilizing a stem structure at the WNV RNA's 3 ′ -end. Here we show that in mammalian cells, AUF1 p45 is consistently modified by arginine methylation of its C terminus. By a combination of different experimental approaches, we can demonstrate that the methyltransferase PRMT1 is necessary and sufficient for AUF1 p45 methylation and that PRMT1 is required for efficient WNV replication. Interestingly, in comparison to the nonmethylated AUF1 p45, the methylated AUF1 p45 aDMA exhibits a significantly increased affinity to the WNV RNA termini. Further data also revealed that the RNA chaperone activity of AUF1 p45 aDMA is improved and the methylated protein stimulates viral RNA synthesis considerably more efficiently than the nonmethylated AUF1 p45. In addition to its destabilizing RNA chaperone activity, we identified an RNA annealing activity of AUF1 p45, which is not affected by methylation. Arginine methylation of AUF1 p45 thus represents a specific determinant of its RNA chaperone activity while functioning as a WNV host factor. Our data suggest that the methylation modifies the conformation of AUF1 p45 and in this way affects its RNA binding and restructuring activities.

show abstract

Section: Discussionmentioning

confidence: 67%

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45

Friedrich

Schmidt

Schierhorn

et al. 2016

RNA

View full text Add to dashboard Cite

show abstract

“…The conflicting results might be due to variations in the included bordering UTRs of the Bici constructs. A regulatory role in the transcription of genes and translation of mRNAs has also been reported for the long UTRs in the genomes of other NNS RNA viruses (65)(66)(67)(68)(69). It will therefore be of interest to determine whether the observed inhibitory effects of certain IR lengths are specific to the gene border containing the long IR or if they can be recapitulated at other EBOV gene borders.…”

Section: Discussionmentioning

confidence: 87%

Analysis of the Highly Diverse Gene Borders in Ebola Virus Reveals a Distinct Mechanism of Transcriptional Regulation

Brauburger

Boehmann

Tsuda

et al. 2014

J Virol

View full text Add to dashboard Cite

Ebola virus (EBOV) belongs IMPORTANCEOur current understanding of EBOV transcription regulation is limited due to the requirement for high-containment conditions to study this highly pathogenic virus. EBOV is thought to share many mechanistic features with well-analyzed prototype nonsegmented negative-sense RNA viruses. A single polymerase entry site at the 3= end of the genome determines that transcription of the genes is mainly controlled by gene order and cis-acting signals found at the gene borders. Here, we examined the regulatory role of the structurally unique EBOV gene borders during viral transcription. Our data suggest that transcriptional regulation in EBOV is highly complex and differs from that in prototype viruses and further the understanding of this most fundamental process in the filovirus replication cycle. Moreover, our results with recombinant EBOVs suggest a novel role of the long IR found in all filovirus genomes during the viral replication cycle.

show abstract

“…We therefore hypothesize that highly-expressed genes like N and P can tolerate some dysregulation without significant negative effects, whereas the intolerance to dysregulation of less-abundant genes like F, H/HN, and L may be an indicator of how stringently-regulated they are. Our studies suggest that the regulatory functions of these intergenic regions in PMVs [21][22][23][24] should be systematically explored in their appropriate genomic contexts, which is now possible using robust and efficient reverse genetics systems.…”

Section: Plos Pathogensmentioning

confidence: 99%

Genome-wide transposon mutagenesis of paramyxoviruses reveals constraints on genomic plasticity

et al. 2020

View full text Add to dashboard Cite

The antigenic and genomic stability of paramyxoviruses remains a mystery. Here, we evaluate the genetic plasticity of Sendai virus (SeV) and mumps virus (MuV), sialic acid-using paramyxoviruses that infect mammals from two Paramyxoviridae subfamilies (Orthoparamyxovirinae and Rubulavirinae). We performed saturating whole-genome transposon insertional mutagenesis, and identified important commonalities: disordered regions in the N and P genes near the 3' genomic end were more tolerant to insertional disruptions; but the envelope glycoproteins were not, highlighting structural constraints that contribute to the restricted antigenic drift in paramyxoviruses. Nonetheless, when we applied our strategy to a fusion-defective Newcastle disease virus (Avulavirinae subfamily), we could select for Frevertants and other insertants in the 5' end of the genome. Our genome-wide interrogation of representative paramyxovirus genomes from all three Paramyxoviridae subfamilies provides a family-wide context in which to explore specific variations within and among paramyxovirus genera and species.

show abstract

Downregulation of Nipah Virus N mRNA Occurs through Interaction between Its 3′ Untranslated Region and hnRNP D

Cited by 19 publications

References 28 publications

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45

Analysis of the Highly Diverse Gene Borders in Ebola Virus Reveals a Distinct Mechanism of Transcriptional Regulation

Genome-wide transposon mutagenesis of paramyxoviruses reveals constraints on genomic plasticity

Contact Info

Product

Resources

About