scholarly journals The amazing diversity of cap-independent translation elements in the 3′-untranslated regions of plant viral RNAs

2007 ◽  
Vol 35 (6) ◽  
pp. 1629-1633 ◽  
Author(s):  
W.A. Miller ◽  
Z. Wang ◽  
K. Treder
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
The Other ◽  
Untranslated Regions ◽  
Viral Rnas ◽  
Initiation Factors ◽  
Translation Factors ◽  
Translation Initiation Factors ◽  
Insight Into ◽  
Independent Translation

Many plant viral RNAs lack the 5′-cap structure that is required on all host mRNAs for interacting with essential translation initiation factors. Instead, uncapped viral RNAs take over the host translation machinery by harbouring sequences that functionally replace the 5′-cap. Recent reports reveal at least eight different classes of CITE (cap-independent translation element) located in the 3′-UTRs (untranslated regions) of various viruses. We describe how the structure and behaviour of each class of element differs from the other classes, suggesting that they recruit translation factors and, ultimately, the ribosome by diverse mechanisms. These results greatly expand our understanding of ways in which mRNAs can recruit ribosomes, and they provide insight into the regulation of virus gene expression.

scholarly journals Dysregulation of Translation Factors EIF2S1, EIF5A and EIF6 in Intestinal-Type Adenocarcinoma (ITAC)

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5649
Author(s):  
Christoph Schatz ◽  
Susanne Sprung ◽  
Volker Schartinger ◽  
Helena Codina-Martínez ◽  
Matt Lechner ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Neoplastic Tissue ◽  
Eukaryotic Translation ◽  
Initiation Factors ◽  
Translation Factors ◽  
Translation Initiation Factors ◽  
Eukaryotic Translation Initiation ◽  
Intestinal Type Adenocarcinoma ◽  
Eukaryotic Translation Initiation Factors ◽  
In Silico Analyses

Intestinal-type adenocarcinoma (ITAC) is a rare cancer of the nasal cavity and paranasal sinuses that occurs sporadically or secondary to exposure to occupational hazards, such as wood dust and leather. Eukaryotic translation initiation factors have been described as promising targets for novel cancer treatments in many cancers, but hardly anything is known about these factors in ITAC. Here we performed in silico analyses, evaluated the protein levels of EIF2S1, EIF5A and EIF6 in tumour samples and non-neoplastic tissue controls obtained from 145 patients, and correlated these results with clinical outcome data, including tumour site, stage, adjuvant radiotherapy and survival. In silico analyses revealed significant upregulation of the translation factors EIF6 (ITGB4BP), EIF5, EIF2S1 and EIF2S2 (p < 0.05) with a higher arithmetic mean expression in ITAC compared to non-neoplastic tissue (NNT). Immunohistochemical analyses using antibodies against EIF2S1 and EIF6 confirmed a significantly different expression at the protein level (p < 0.05). In conclusion, this work identifies the eukaryotic translation initiation factors EIF2S1 and EIF6 to be significantly upregulated in ITAC. As these factors have been described as promising therapeutic targets in other cancers, this work identifies candidate therapeutic targets in this rare but often deadly cancer.

scholarly journals Unbiased screen of human transcriptome reveals an unexpected role of 3ʹUTRs in translation initiation

2021 ◽  
Author(s):  
Zefeng Wang ◽  
Yun Yang ◽  
Xiaojuan Fan ◽  
Yanwen Ye ◽  
Chuyun Chen ◽  
...  
Keyword(s):  
Cell Growth ◽  
Translation Initiation ◽  
Human Transcriptome ◽  
Initiation Factors ◽  
Regulatory Mode ◽  
Translation Initiation Factors ◽  
Eukaryotic Mrnas ◽  
Independent Translation

Although most eukaryotic mRNAs require a 5ʹ-cap for translation initiation, some can also be translated through a poorly studied cap-independent pathway. Here we developed a circRNA-based system and unbiasedly identified more than 10,000 sequences in the human transcriptome that contain Cap-independent Translation Initiators (CiTIs). Surprisingly, most of the identified CiTIs are located in 3ʹUTRs, which mainly promote translation initiation in mRNAs bearing highly structured 5ʹUTR. Mechanistically, CiTI recruits several translation initiation factors including eIF3 and DHX29, which in turn unwind 5ʹUTR structures and facilitate ribosome scanning. Functionally, we showed that the translation of HIF1A mRNA, an endogenous DHX29 target, is antagonistically regulated by its 5ʹUTR structure and a new 3ʹ-CiTI in response to hypoxia. Therefore, deletion of 3ʹ-CiTI suppresses cell growth in hypoxia and tumor progression in vivo. Collectively, our study uncovers a new regulatory mode for translation where the 3ʹUTR actively participate in the translation initiation.

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