scholarly journals RNA-binding Protein HuR Interacts with Thrombomodulin 5′Untranslated Region and Represses Internal Ribosome Entry Site–mediated Translation under IL-1β Treatment

2008 ◽  
Vol 19 (9) ◽  
pp. 3812-3822 ◽  
Author(s):  
Chiu-Hung Yeh ◽  
Liang-Yi Hung ◽  
Chin Hsu ◽  
Shu-Yun Le ◽  
Pin-Tse Lee ◽  
...  
Keyword(s):  
Protein Expression ◽  
Internal Ribosome Entry Site ◽  
Untranslated Region ◽  
Protein C ◽  
Rna Binding ◽  
Activated Protein C ◽  
Critical Factor ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Sepsis And Septic Shock

Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis.

scholarly journals Efficient Translation Initiation Directed by the 900-Nucleotide-Long and GC-Rich 5′ Untranslated Region of the Human Retrotransposon LINE-1 mRNA Is Strictly Cap Dependent Rather than Internal Ribosome Entry Site Mediated

2007 ◽  
Vol 27 (13) ◽  
pp. 4685-4697 ◽  
Author(s):  
Sergey E. Dmitriev ◽  
Dmitri E. Andreev ◽  
Ilya M. Terenin ◽  
Ivan A. Olovnikov ◽  
Vladimir S. Prassolov ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Internal Ribosome Entry Site ◽  
Untranslated Region ◽  
High Efficiency ◽  
Rna Binding ◽  
Cultured Cells ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Cellular Mrnas ◽  
Internal Initiation

ABSTRACT Retrotransposon L1 is a mobile genetic element of the LINE family that is extremely widespread in the mammalian genome. It encodes a dicistronic mRNA, which is exceptionally rare among eukaryotic cellular mRNAs. The extremely long and GC-rich L1 5′ untranslated region (5′UTR) directs synthesis of numerous copies of RNA-binding protein ORF1p per mRNA. One could suggest that the 5′UTR of L1 mRNA contained a powerful internal ribosome entry site (IRES) element. Using transfection of cultured cells with the polyadenylated monocistronic (L1 5′UTR-Fluc) or bicistronic (Rluc-L1 5′UTR-Fluc) RNA constructs, capped or uncapped, it has been firmly established that the 5′UTR of L1 does not contain an IRES. Uncapping reduces the initiation activity of the L1 5′UTR to that of background. Moreover, the translation is inhibited by upstream AUG codons in the 5′UTR. Nevertheless, this cap-dependent initiation activity of the L1 5′UTR was unexpectedly high and resembles that of the beta-actin 5′UTR (84 nucleotides long). Strikingly, the deletion of up to 80% of the nucleotide sequence of the L1 5′UTR, with most of its stem loops, does not significantly change its translation initiation efficiency. These data can modify current ideas on mechanisms used by 40S ribosomal subunits to cope with complex 5′UTRs and call into question the conception that every long GC-rich 5′UTR working with a high efficiency has to contain an IRES. Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event.

Does HIV-1 mRNA 5'-untranslated region bear an internal ribosome entry site?

Biochimie ◽  
2016 ◽  
Vol 121 ◽  
pp. 228-237 ◽  
Author(s):  
Victoria V. Smirnova ◽  
Ilya M. Terenin ◽  
Anastasia A. Khutornenko ◽  
Dmitri E. Andreev ◽  
Sergey E. Dmitriev ◽  
...  
Keyword(s):  
Internal Ribosome Entry Site ◽  
Untranslated Region ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Hiv 1

The 5′ untranslated region of the maize alcohol dehydrogenase gene contains an internal ribosome entry site

Gene ◽  
2008 ◽  
Vol 420 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Eugenia S. Mardanova ◽  
Ludmila A. Zamchuk ◽  
Maxim V. Skulachev ◽  
Nikolai V. Ravin
Keyword(s):  
Alcohol Dehydrogenase ◽  
Internal Ribosome Entry Site ◽  
Untranslated Region ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Dehydrogenase Gene

scholarly journals Roles of the 5′ Untranslated Region of Nonprimate Hepacivirus in Translation Initiation and Viral Replication

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Tomohisa Tanaka ◽  
Teruhime Otoguro ◽  
Atsuya Yamashita ◽  
Hirotake Kasai ◽  
Takasuke Fukuhara ◽  
...  
Keyword(s):  
Viral Replication ◽  
Internal Ribosome Entry Site ◽  
Untranslated Region ◽  
Rna Stability ◽  
Specific Region ◽  
Entry Site ◽  
Subgenomic Replicon ◽  
Independent Manner ◽  
Internal Ribosome Entry ◽  
Domain I

ABSTRACTThe 5′ untranslated region (UTR) of hepatitis C virus (HCV), which is composed of four domains (I, II, III, and IV) and a pseudoknot, is essential for translation and viral replication. Equine nonprimate hepacivirus (EHcV) harbors a 5′ UTR consisting of a large 5′-terminal domain (I); three additional domains (I′, II, and III), which are homologous to domains I, II, and III, respectively, of HCV; and a pseudoknot, in the order listed. In this study, we investigated the roles of the EHcV 5′ UTR in translation and viral replication. The internal ribosome entry site (IRES) activity of the EHcV 5′ UTR was lower than that of the HCV 5′ UTR in several cell lines due to structural differences in domain III. Domains I and III of EHcV were functional in the HCV 5′ UTR in terms of IRES activity and the replication of the subgenomic replicon (SGR), although domain II was not exchangeable between EHcV and HCV for SGR replication. Furthermore, the region spanning domains I and I′ of EHcV (the 5′-proximal EHcV-specific region) improved RNA stability and provided the HCV SGR with microRNA 122 (miR-122)-independent replication capability, while EHcV domain I alone improved SGR replication and RNA stability irrespective of miR-122. These data suggest that the region spanning EHcV domains I and I′ improves RNA stability and viral replication regardless of miR-122 expression. The 5′-proximal EHcV-specific region may represent an inherent mechanism to facilitate viral replication in nonhepatic tissues.IMPORTANCEEHcV is the closest viral homolog to HCV among other hepaciviruses. HCV exhibits a narrow host range and liver-specific tropism, while epidemiological reports suggest that EHcV infects the liver and respiratory organs in horses, donkeys, and dogs. However, the mechanism explaining the differences in host or organ tropism between HCV and EHcV is unknown. In this study, our data suggest that the 5′ untranslated region (UTR) of EHcV is composed of an internal ribosome entry site (IRES) element that is functionally exchangeable with HCV IRES elements. Furthermore, the 5′-proximal EHcV-specific region enhances viral replication and RNA stability in a miR-122-independent manner. Our data suggest that the region upstream of domain II in the EHcV 5′ UTR contributes to the differences in tissue tropism observed between these hepaciviruses.

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