scholarly journals Impact of uORFs in mediating regulation of translation in stress conditions

Author(s):  
Simone G. Moro ◽  
Cedric Hermans ◽  
Jorge Ruiz-Orera ◽  
M. Mar Albà

Abstract Background: A large fraction of genes contain upstream ORFs (uORFs) in the 5' untranslated region (5'UTR). The translation of uORFs can inhibit the translation of the main coding sequence, for example by causing premature dissociation of the two ribosomal units or ribosome stalling. However, it is currently unknown if most uORFs are inhibitory or if this activity is restricted to specific cases. Here we interrogate ribosome profiling data from three different stress experiments in yeast to address this question. Results: By comparing ribosome occupancies in different conditions and experiments we obtain strong evidence that, in comparison to primary coding sequences (CDS), which undergo translational arrest during stress, the translation of uORFs is mostly unaffected by changes in the environment. As a result the relative abundance of uORF-encoded peptides increases during stress. In general, the changes in the translational efficiency of regions containing uORFs do not seem to affect downstream translation. The exception are uORFs found in a subset of genes that are strongly up-regulated at the level of translation during stress; these uORFs tend to be translated at lower levels during stress than in optimal growth conditions, facilitating the translation of the CDS during stress. We find new examples of uORF-mediated regulation of translation, including the Gcn4 functional homologue fil1 and ubi4 genes in S. pombe.Conclusion: We find evidence that the relative amount of uORF-encoded peptides increases during stress. The increased translation of uORFs is however uncoupled from the general CDS translational repression observed during stress. In a subset of genes that encode proteins that need to be rapidly synthesized upon stress uORFs act as translational switches.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Simone G. Moro ◽  
Cedric Hermans ◽  
Jorge Ruiz-Orera ◽  
M. Mar Albà

Abstract Background A large fraction of genes contains upstream ORFs (uORFs) in the 5′ untranslated region (5’UTR). The translation of uORFs can inhibit the translation of the main coding sequence, for example by causing premature dissociation of the two ribosomal units or ribosome stalling. However, it is currently unknown if most uORFs are inhibitory or if this activity is restricted to specific cases. Here we interrogate ribosome profiling data from three different stress experiments in yeast to gain novel insights into this question. Results By comparing ribosome occupancies in different conditions and experiments we obtain strong evidence that, in comparison to primary coding sequences (CDS), which undergo translational arrest during stress, the translation of uORFs is mostly unaffected by changes in the environment. As a result, the relative abundance of uORF-encoded peptides increases during stress. In general, the changes in the translational efficiency of regions containing uORFs do not seem to affect downstream translation. The exception are uORFs found in a subset of genes that are significantly up-regulated at the level of translation during stress; these uORFs tend to be translated at lower levels in stress conditions than in optimal growth conditions, facilitating the translation of the CDS during stress. We find new examples of uORF-mediated regulation of translation, including the Gcn4 functional homologue fil1 and ubi4 genes in S. pombe. Conclusion We find evidence that the relative amount of uORF-encoded peptides increases during stress. The increased translation of uORFs is however uncoupled from the general CDS translational repression observed during stress. In a subset of genes that encode proteins that need to be rapidly synthesized upon stress uORFs act as translational switches.


2019 ◽  
Author(s):  
Gabriele Baniulyte ◽  
Joseph T. Wade

AbstractLong 5′ UTRs in bacteria often contain regulatory elements that modulate expression of the downstream gene in response to environmental stimuli. In most examples of such regulation, the mechanism involves switching between alternative 5′ UTR RNA structures that impact transcription, stability, or translation of the mRNA. Here, we show that transcription of theEscherichia coli topAIgene is prematurely terminated by the termination factor Rho under standard laboratory growth conditions, and that this occurs as a result of translational repression. Regulation oftopAItranslation is controlled by a sensory ORF,toiL, located within thetopAI5′ UTR. We show that ribosomes translatingtoiLstall in a sequence-specific manner in the presence of specific ribosome-targeting antibiotics. Ribosome stalling attoiLinduces conformational changes in the RNA structure of thetopAI5′ UTR, unmasking thetopAIribosome-binding site, thereby relieving translational repression and preventing premature transcription termination. Thus,toiLacts as a sensor of translation stress, leading to regulation oftopAIat both the translational and transcriptional levels.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.


1992 ◽  
Vol 12 (9) ◽  
pp. 3827-3833 ◽  
Author(s):  
T H Adams ◽  
W A Hide ◽  
L N Yager ◽  
B N Lee

In contrast to many other cases in microbial development, Aspergillus nidulans conidiophore production initiates primarily as a programmed part of the life cycle rather than as a response to nutrient deprivation. Mutations in the acoD locus result in "fluffy" colonies that appear to grow faster than the wild type and proliferate as undifferentiated masses of vegetative cells. We show that unlike wild-type strains, acoD deletion mutants are unable to make conidiophores under optimal growth conditions but can be induced to conidiate when growth is nutritionally limited. The requirement for acoD in conidiophore development occurs prior to activation of brlA, a primary regulator of development. The acoD transcript is present both in vegetative hyphae prior to developmental induction and in developing cultures. However, the effects of acoD mutations are detectable only after developmental induction. We propose that acoD activity is primarily controlled at the posttranscriptional level and that it is required to direct developmentally specific changes that bring about growth inhibition and activation of brlA expression to result in conidiophore development.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Lyudmila P. Trenozhnikova ◽  
Almagul K. Khasenova ◽  
Assya S. Balgimbaeva ◽  
Galina B. Fedorova ◽  
Genrikh S. Katrukha ◽  
...  

We describe the actinomycete strain IMV-70 isolated from the soils of Kazakhstan, which produces potent antibiotics with high levels of antibacterial activity. After the research of its morphological, chemotaxonomic, and cultural characteristics, the strain with potential to be developed further as a novel class of antibiotics with chemotherapeutics potential was identified asStreptomycessp. IMV-70. In the process of fermentation, the strainStreptomycesspp. IMV-70 produces the antibiotic no. 70, which was isolated from the culture broth by extraction with organic solvents. Antibiotic compound no. 70 was purified and separated into individual components by HPLC, TLC, and column chromatography methods. The main component of the compound is the antibiotic 70-A, which was found to be identical to the peptolide etamycin A. Two other antibiotics 70-B and 70-C have never been described and therefore are new antibiotics. The physical-chemical and biological characteristics of these preparations were described and further researched. Determination of the optimal growth conditions to cultivate actinomycete-producer strain IMV-70 and development of methods to isolate, purify, and accumulate preparations of the new antibiotic no. 70 enable us to research further the potential of this new class of antibiotics.


1974 ◽  
Vol 20 (10) ◽  
pp. 1403-1409 ◽  
Author(s):  
B. G. Foster ◽  
Mary O. Hanna

Aeromonas proteolytica was grown for various time periods in nutrient broth, tryptic soy broth, a semisynthetic medium, and 1 and 5% peptone under different conditions involving temperature and in continuous shake and stationary flasks. The cell-free culture filtrates were tested for hemolytic, endopeptidase, and dermonecrotic activity and optimal growth conditions for their production were determined. The dermonecrotic activity and endopeptidase activity was found to be parallel in all tests, while hemolysin was independent of the other two. Studies on the thermal stability of the culture filtrate revealed that hemolysin and dermonecrotic and endopeptidase activity were destroyed at 70 °C for 30 min. Fractionation of the filtrate by Sephadex G-200 resolved three peaks at 280 nm. Peak I was inactive; peak II contained endopeptidase and dermonecrotic and hemolytic activity; peak III contained pigment and hemolysin. Evidence is presented that the endopeptidase and dermonecrotic substance found in the cell-free filtrates of A. proteolytica grown medium appear at the same time and thus may be the same entity.


Author(s):  
Ben Hadj-Daoud H ◽  
◽  
Ben Salem I ◽  
Boughalleb-M’Hamdi N ◽  
◽  
...  

Background: Colletotrichum gloeosporioides is important plant pathogens on a wide range of plant hosts such as citrus causing pre- or post-harvest infections as anthracnose, post-bloom fruit drop, tearstain and stem-end rot on fruit, or wither-tip of twigs. Method: The optimization of growth conditions of this pathogen was performed (solid media, temperature, pH and water potential under laboratory experiments). Results: Our results revealed that the maximum radial growth of C. gloeosporioides was recorded on SDA medium. All isolates were able to grow on PDA at temperatures of 15 and 30°C (over 0.7cm/day). Optimal growth radial was recorded at pH 5, 6, 7 and 8. Similar responses were obtained with both salt types, but, in general, C. gloeosporioides was more tolerant to KCl than NaCl. Conclusion: Studies of cultural, morphological traits of the pathogen are prominent to understand the response of the pathogen in different environmental and nutritional conditions.


2010 ◽  
Vol 60 (12) ◽  
pp. 2996-3001 ◽  
Author(s):  
Shi-Ping Tian ◽  
Yong-Xia Wang ◽  
Bin Hu ◽  
Xiao-Xia Zhang ◽  
Wei Xiao ◽  
...  

A novel alkaliphilic, halotolerant, rod-shaped bacterium, designated strain YIM CH208T, was isolated from a soda lake in Yunnan, south-west China. The taxonomy of strain YIM CH208T was investigated by a polyphasic approach. Strain YIM CH208T was Gram-negative, strictly aerobic and non-motile and formed red colonies. Optimal growth conditions were 28 °C, pH 8.5 and 0.5–2.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the isolate formed a distinct line within a clade containing the genus Echinicola in the phylum Bacteroidetes and was related to the species Echinicola pacifica and Rhodonellum psychrophilum, with sequence similarity of 91.7 and 91.6 % to the respective type strains. The DNA G+C content was 45.1 mol%. The major respiratory quinone was menaquinone-7 (MK-7). The predominant cellular fatty acids were iso-C17 : 1 ω9c (19.9 %), C15 : 0 3-OH (12.1 %), iso-C17 : 0 3-OH (11.3 %), summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c; 10.7 %) and C17 : 1 ω6c (8.7 %). On the basis of the phenotypic, chemotaxonomic and phylogenetic data, strain YIM CH208T represents a novel species of a new genus, for which the name Litoribacter ruber gen. nov., sp. nov. is proposed. The type strain of Litoribacter ruber is YIM CH208T (=ACCC 05414T =KCTC 22899T).


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