RNA structure-based ribosome recruitment: Lessons from the <i>Dicistroviridae</i> intergenic region IRESes

Pfingsten, Jennifer S.; Kieft, Jeffrey S.

doi:10.1261/rna.987808

Cited by 26 publications

(24 citation statements)

References 77 publications

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“…This approach has been applied to the cricket paralysis virus IRES RNA bound to ribosomes in cryoelectron densities at 7.3 Å (Schuler et al 2006). The resulting model, obtained before crystallography (Pfingsten et al 2006), agrees very well with the structure of the IRES RNA structure alone (Pfingsten and Kieft 2008).…”

Section: Modeling and Fitting Into Medium To Low Resolution Electron supporting

confidence: 65%

Predicting and Modeling RNA Architecture

Westhof¹,

Masquida²,

Jossinet³

2010

Cold Spring Harbor Perspectives in Biology

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SUMMARYA general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Despite the extensive molecular neutrality observed in RNA structures, specificity in RNA folding is achieved through global constraints like lengths of helices, coaxiality of helical stacks, and structures adopted at the junctions of helices. The Assemble integrated suite of computer tools allows for sequence and structure analysis as well as interactive modeling by homology or ab initio assembly with possibilities for fitting within electronic density maps. The local key role of non-Watson-Crick pairs guides RNA architecture formation and offers metrics for assessing the accuracy of three-dimensional models in a more useful way than usual root mean square deviation (RMSD) values.

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Section: Modeling and Fitting Into Medium To Low Resolution Electron supporting

confidence: 65%

Predicting and Modeling RNA Architecture

Westhof¹,

Masquida²,

Jossinet³

2010

Cold Spring Harbor Perspectives in Biology

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“…Dicistroviruses have been shown to replicate and be pathogenic in insects (10,37). The internal ribosomal entry site between the two cistronic segments can act as a powerful promoter in mammalian cells (28). However, reports of viral replication within mammalian cell lines are contradictory; one group has demonstrated the replication of a dicistrovirus, Taura syndrome virus, in human cell lines (3), while another has failed to reproduce Taura syndrome virus growth in mammalian cell lines (27).…”

Section: Discussionmentioning

confidence: 99%

Metagenomic Analyses of Viruses in Stool Samples from Children with Acute Flaccid Paralysis

Victoria

Kapoor

et al. 2009

J Virol

343

345

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We analyzed viral nucleic acids in stool samples collected from 35 South Asian children with nonpolio acute flaccid paralysis (AFP). Sequence-independent reverse transcription and PCR amplification of capsid-protected, nuclease-resistant viral nucleic acids were followed by DNA sequencing and sequence similarity searches. Limited Sanger sequencing (35 to 240 subclones per sample) identified an average of 1.4 distinct eukaryotic viruses per sample, while pyrosequencing yielded 2.6 viruses per sample. In addition to bacteriophage and plant viruses, we detected known enteric viruses, including rotavirus, adenovirus, picobirnavirus, and human enterovirus species A (HEV-A) to HEV-C, as well as numerous other members of the Picornaviridae family, including parechovirus, Aichi virus, rhinovirus, and human cardiovirus. The viruses with the most divergent sequences relative to those of previously reported viruses included members of a novel Picornaviridae genus and four new viral species (members of the Dicistroviridae, Nodaviridae, and Circoviridae families and the Bocavirus genus). Samples from six healthy contacts of AFP patients were similarly analyzed and also contained numerous viruses, particularly HEV-C, including a potentially novel Enterovirus genotype. Determining the prevalences and pathogenicities of the novel genotypes, species, genera, and potential new viral families identified in this study in different demographic groups will require further studies with different demographic and patient groups, now facilitated by knowledge of these viral genomes.

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“…The mechanisms of the hepatitis C virus (HCV) and CrPV IGR IRESs represent the simplest and best studied IRESs to date. Interestingly, although they are very different in sequence and structure (Spahn et al 2001(Spahn et al , 2004Boehringer et al 2005;Pfingsten et al 2006;Schuler et al 2006;Costantino et al 2008;Pfingsten and Kieft 2008), they share some similarities in their mechanism for binding ribosomes. In vitro they can both bind directly to 40S subunits, occupy the E-site of the ribosome, result in similar conformational changes of the 40S subunit prior to 60S joining , and initiate protein synthesis in the absence of any initiation factors (Jan et al 2003;Pestova and Hellen 2003;Lancaster et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Translation initiation factors are not required for Dicistroviridae IRES function in vivo

Deniz¹,

Lenarcic²,

Landry³

et al. 2009

RNA

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The cricket paralysis virus (CrPV) intergenic region (IGR) internal ribosome entry site (IRES) uses an unusual mechanism of initiating translation, whereby the IRES occupies the P-site of the ribosome and the initiating tRNA enters the A-site. In vitro experiments have demonstrated that the CrPV IGR IRES is able to bind purified ribosomes and form 80S complexes capable of synthesizing small peptides in the absence of any translation initiation factors. These results suggest that initiation by this IRES is factor-independent. To determine whether the IGR IRES functions in the absence of initiation factors in vivo, we assayed IGR IRES activity in various yeast strains harboring mutations in canonical translation initiation factors. We used a dicistronic reporter assay in yeast to determine whether the CrPV IGR IRES is able to promote translation sufficient to support growth in the presence of various deletions or mutations in translation initiation factors. Using this assay, we have previously shown that the CrPV IGR IRES functions efficiently in yeast when ternary complexes (eIF2 d GTP d initiator tRNA met ) are reduced. Here, we demonstrate that the CrPV IGR IRES activity does not require the eukaryotic initiation factors eIF4G1 or eIF5B, and it is enhanced when eIF2B, the eIF3b subunit of eIF3, or eIF4E are impaired. Taken together, these data support a model in which the CrPV IGR IRES is capable of initiating protein synthesis in the absence of any initiation factors in vivo, and suggests that the CrPV IGR IRES initiates translation by directly recruiting the ribosomal subunits in vivo.

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RNA structure-based ribosome recruitment: Lessons from the Dicistroviridae intergenic region IRESes

Cited by 26 publications

References 77 publications

Predicting and Modeling RNA Architecture

Predicting and Modeling RNA Architecture

Metagenomic Analyses of Viruses in Stool Samples from Children with Acute Flaccid Paralysis

Translation initiation factors are not required for Dicistroviridae IRES function in vivo

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