IRESite—a tool for the examination of viral and cellular internal ribosome entry sites

Mokrejš, Martin; Mašek, Tomáš; Vopálenský, Václav; Hlubuček, Petr; Delbos, Philippe; Pospíšek, Martin

doi:10.1093/nar/gkp981

Cited by 146 publications

(144 citation statements)

References 17 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…According to the IRESite database, although there aren't similarities with known virus IRES motifs, there are a few eukaryotic genes whose 5'UTR contains proven cellular IRES and shares a similarity with the sequence of putative PTCH1b IRES motif. 63 More interestingly, the highest similarity lies in the presence of CGGrepeat element. Such genes, having at least 3 CGG repeats within their IRES motifs, include previously mentioned FMR1 gene, jun proto-oncogene (JUN), ornithine decarboxylase 1 (ODC1), B-cell CLL/lymphoma 2 (BCL2), and BCL2-associated athanogene (BAG1).…”

Section: Discussionmentioning

confidence: 96%

Regulation of humanPTCH1bexpression by different 5' untranslated regioncis-regulatory elements

et al. 2015

View full text Add to dashboard Cite

Inga (2015) Regulation of human PTCH1b expression by different 5' untranslated region cis-regulatory elements, RNA Biology, 12:3, 290-304, DOI: 10.1080/15476286.2015 PTCH1 gene codes for a 12-pass transmembrane receptor with a negative regulatory role in the Hedgehog-Gli signaling pathway. PTCH1 germline mutations cause Gorlin syndrome, a disorder characterized by developmental abnormalities and tumor susceptibility. The autosomal dominant inheritance, and the evidence for PTCH1 haploinsufficiency, suggests that fine-tuning systems of protein patched homolog 1 (PTC1) levels exist to properly regulate the pathway. Given the role of 5' untranslated region (5'UTR) in protein expression, our aim was to thoroughly explore cis-regulatory elements in the 5'UTR of PTCH1 transcript 1b. The (CGG) n polymorphism was the main potential regulatory element studied so far but with inconsistent results and no clear association between repeat number and disease risk. Using luciferase reporter constructs in human cell lines here we show that the number of CGG repeats has no strong impact on gene expression, both at mRNA and protein levels. We observed variability in the length of 5'UTR and changes in abundance of the associated transcripts after pathway activation. We show that upstream AUG codons (uAUGs) present only in longer 5'UTRs could negatively regulate the amount of PTC1 isoform L (PTC1-L). The existence of an internal ribosome entry site (IRES) observed using different approaches and mapped in the region comprising the CGG repeats, would counteract the effect of the uAUGs and enable synthesis of PTC1-L under stressful conditions, such as during hypoxia. Higher relative translation efficiency of PTCH1b mRNA in HEK 293T cultured hypoxia was observed by polysomal profiling and Western blot analyses. All our results point to an exceptionally complex and so far unexplored role of 5'UTR PTCH1b cis-element features in the regulation of the Hedgehog-Gli signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 96%

Regulation of humanPTCH1bexpression by different 5' untranslated regioncis-regulatory elements

et al. 2015

View full text Add to dashboard Cite

show abstract

“…IRES have been found in the RNA genomes of different viruses and in some cellular mRNA 49 . They have been divided in four groups on the basis of their predicted secondary structure and on their requirements for initiation factors and other cellular factors 50 .…”

Section: Discussionmentioning

confidence: 99%

Structure of the full-length HCV IRES in solution

et al. 2013

View full text Add to dashboard Cite

The 5 0 -untranslated region of the hepatitis C virus genome contains an internal ribosome entry site (IRES) that initiates cap-independent translation of the viral RNA. Until now, the structural characterization of the entire (IRES) remained limited to cryo-electron microscopy reconstructions of the (IRES) bound to different cellular partners. Here we report an atomic model of free full-length hepatitis C virus (IRES) refined by selection against small-angle X-ray scattering data that incorporates the known structures of different fragments. We found that an ensemble of conformers reproduces small-angle X-ray scattering data better than a single structure suggesting in combination with molecular dynamics simulations that the hepatitis C virus (IRES) is an articulated molecule made of rigid parts that move relative to each other. Principal component analysis on an ensemble of physically accessible conformers of hepatitis C virus (IRES) revealed dominant collective motions in the molecule, which may underlie the conformational changes occurring in the (IRES) molecule upon formation of the initiation complex.

show abstract

“…34 In the other branch (3) we scan our UTRs in order to identify cis-elements that may be contained therein. Again, we employ both experimentally validated data (A), coming from IRESite 27 and possibly other sources, and computationally predicted annotations, obtained through UTRsite, 12 AREsite, 26 SIREs 33 and others. Once data collection is completed, we can move to the next step (4): building a network including our initial genes and all the factors identified until this point as regulators.…”

Section: Designing a Discovery Pipelinementioning

confidence: 99%

“…Available databases are focused mainly on UTRs annotation, 12,13 RBP-target interactions, 14,15 ncRNAs, [16][17][18][19][20][21][22][23][24] of which miRNAtarget interactions are the greater part, [16][17][18][19][20] with a limited number of resources focusing on lncRNAs, 22,23 and cis-elements. [25][26][27][28][29][30] Furthermore, a small number of resources integrating different data types is available. 12,13,31 Predictive tools also exist, in particular for cis-elements pattern-based search 32,33 and ncRNAs.…”

mentioning

confidence: 99%