scholarly journals Ribosome profiling in Mycobacterium tuberculosis reveals robust leaderless translation

2020 ◽  
Author(s):  
Elizabeth B. Sawyer ◽  
Jody E. Phelan ◽  
Taane G. Clark ◽  
Teresa Cortes
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Translation Initiation ◽  
Persistent Infection ◽  
Translational Regulation ◽  
Nutrient Starvation ◽  
Ribosome Profiling ◽  
Initiation Of Translation ◽  
Bacterial Translation Initiation ◽  
Bacterial Translation

AbstractMycobacterium tuberculosis, which causes tuberculosis, expresses a large proportion of leaderless transcripts lacking the canonical bacterial translation initiation signals. The role leaderless genes play in the physiology of this pathogen, which can undergo prolonged periods of non-replicating persistence in the host, is currently unknown. We have previously demonstrated that levels of leaderless transcription increase under conditions of nutrient starvation. However, little is known about the implications of this for persistent infection. Here, we performed ribosome profiling to characterise the translational landscape of M. tuberculosis in vitro. Our data reveals robust leaderless translation in the pathogen and points towards different mechanisms for their initiation of translation compared to canonical Shine-Dalgarno genes. Furthermore, under conditions of nutrient starvation, we found a significant global up-regulation of leaderless genes in the translatome. Our data represents a rich resource for others seeking to understand translational regulation not only in M. tuberculosis but in bacterial pathogens.

scholarly journals Translation initiation factor 4A from Saccharomyces cerevisiae: analysis of residues conserved in the D-E-A-D family of RNA helicases.

1991 ◽  
Vol 11 (7) ◽  
pp. 3463-3471 ◽  
Author(s):  
S R Schmid ◽  
P Linder
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Clear Correlation ◽  
Temperature Sensitive ◽  
Rna Helicases ◽  
Initiation Of Translation

The eukaryotic translation initiation factor 4A (eIF-4A) possesses an in vitro helicase activity that allows the unwinding of double-stranded RNA. This activity is dependent on ATP hydrolysis and the presence of another translation initiation factor, eIF-4B. These two initiation factors are thought to unwind mRNA secondary structures in preparation for ribosome binding and initiation of translation. To further characterize the function of eIF-4A in cellular translation and its interaction with other elements of the translation machinery, we have isolated mutations in the TIF1 and TIF2 genes encoding eIF-4A in Saccharomyces cerevisiae. We show that three highly conserved domains of the D-E-A-D protein family, encoding eIF-4A and other RNA helicases, are essential for protein function. Only in rare cases could we make a conservative substitution without affecting cell growth. The mutants show a clear correlation between their growth and in vivo translation rates. One mutation that results in a temperature-sensitive phenotype reveals an immediate decrease in translation activity following a shift to the nonpermissive temperature. These in vivo results confirm previous in vitro data demonstrating an absolute dependence of translation on the TIF1 and TIF2 gene products.

scholarly journals Implications of the Use of Eukaryotic Translation Initiation Factor 5A (eIF5A) for Prognosis and Treatment of Hepatocellular Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Felix H. Shek ◽  
Sarwat Fatima ◽  
Nikki P. Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Initiation Of Translation ◽  
Eukaryotic Translation Initiation ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a primary liver malignancy and accounts for most of the total liver cancer cases. Lack of treatment options and late diagnosis contribute to high mortality rate of HCC. In eukaryotes, translation of messenger RNA (mRNA) to protein is a key process in protein biosynthesis in which initiation of translation involves interaction of different eukaryotic translation initiation factors (eIFs), ribosome subunits and mRNAs. Eukaryotic translation initiation factor 5A (eIF5A) is one of the eIFs involved in translation initiation and eIF5A2, one of its isoforms, is upregulated in various cancers including HCC as a result of chromosomal instability, where it resides. In HCC, eIF5A2 expression is associated with adverse prognosis such as presence of tumor metastasis and venous infiltration. Based on eIF5A2 functional studies, suppressing eIF5A2 expression by short interfering RNA alleviates the tumorigenic properties of HCC cellsin vitrowhile ectopic expression of eIF5A2 enhances the aggressiveness of HCC cellsin vivoandin vitroby inducing epithelial-mesenchymal transition. In conclusion, eIF5A2 is a potential prognostic marker as well as a therapeutic target for HCC.

scholarly journals A Conserved Structural Motif at the N Terminus of Bacterial Translation Initiation Factor IF2

2003 ◽  
Vol 278 (18) ◽  
pp. 16320-16328 ◽  
Author(s):  
Brian Søgaard Laursen ◽  
Kim Kusk Mortensen ◽  
Hans Uffe Sperling-Petersen ◽  
David W. Hoffman
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Structural Motif ◽  
Initiation Factor ◽  
N Terminus ◽  
Bacterial Translation Initiation ◽  
Bacterial Translation

scholarly journals InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0239354
Author(s):  
Lindsay Flint ◽  
Aaron Korkegian ◽  
Tanya Parish
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Nutrient Starvation ◽  
Cell Wall Biosynthesis

We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activity in vitro and in vivo and targets cell wall biosynthesis via inhibition of InhA. The overall aim of this study was to determine whether InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis. We tested the ability of two molecules of the diazaborine series to kill non-replicating M. tuberculosis in the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicating M. tuberculosis.

scholarly journals uORFs: Important Cis-Regulatory Elements in Plants

2020 ◽  
Vol 21 (17) ◽  
pp. 6238
Author(s):  
Ting Zhang ◽  
Anqi Wu ◽  
Yaping Yue ◽  
Yu Zhao
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Translational Regulation ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Post Translational Modification ◽  
Cis Acting ◽  
Eukaryotic Mrnas

Gene expression is regulated at many levels, including mRNA transcription, translation, and post-translational modification. Compared with transcriptional regulation, mRNA translational control is a more critical step in gene expression and allows for more rapid changes of encoded protein concentrations in cells. Translation is highly regulated by complex interactions between cis-acting elements and trans-acting factors. Initiation is not only the first phase of translation, but also the core of translational regulation, because it limits the rate of protein synthesis. As potent cis-regulatory elements in eukaryotic mRNAs, upstream open reading frames (uORFs) generally inhibit the translation initiation of downstream major ORFs (mORFs) through ribosome stalling. During the past few years, with the development of RNA-seq and ribosome profiling, functional uORFs have been identified and characterized in many organisms. Here, we review uORF identification, uORF classification, and uORF-mediated translation initiation. More importantly, we summarize the translational regulation of uORFs in plant metabolic pathways, morphogenesis, disease resistance, and nutrient absorption, which open up an avenue for precisely modulating the plant growth and development, as well as environmental adaption. Additionally, we also discuss prospective applications of uORFs in plant breeding.

Mapping the Active Sites of Bacterial Translation Initiation Factor IF3

2003 ◽  
Vol 331 (3) ◽  
pp. 541-556 ◽  
Author(s):  
Dezemona Petrelli ◽  
Cristiana Garofalo ◽  
Matilde Lammi ◽  
Roberto Spurio ◽  
Cynthia L Pon ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Active Sites ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Bacterial Translation Initiation ◽  
Bacterial Translation
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