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

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Simone G. Moro ◽  
Cedric Hermans ◽  
Jorge Ruiz-Orera ◽  
M. Mar Albà
Keyword(s):  
Large Fraction ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Ribosome Profiling ◽  
Stress Conditions ◽  
Translational Repression ◽  
Translational Efficiency ◽  
Ribosome Stalling ◽  
Regulation Of Translation ◽  
Translational Arrest

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.

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

2021 ◽  
Author(s):  
Simone G. Moro ◽  
Cedric Hermans ◽  
Jorge Ruiz-Orera ◽  
M. Mar Albà
Keyword(s):  
Untranslated Region ◽  
Large Fraction ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Ribosome Profiling ◽  
Translational Repression ◽  
Translational Efficiency ◽  
Ribosome Stalling ◽  
Regulation Of Translation ◽  
Translational Arrest

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.

Water and Temperature Stress Impact Fitness of Acetohydroxyacid Synthase–Inhibiting Herbicide-Resistant Populations of Eastern Black Nightshade (Solanum ptychanthum)

Weed Science ◽  
2011 ◽  
Vol 59 (3) ◽  
pp. 341-348 ◽  
Author(s):  
Jamshid Ashigh ◽  
François J. Tardif
Keyword(s):  
Seed Production ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Stress Conditions ◽  
Acetohydroxyacid Synthase ◽  
Eastern Black Nightshade ◽  
Black Nightshade ◽  
Reproductive Ability ◽  
Temperature Regimes ◽  
The Impact

Many substitutions in the herbicide target enzyme acetohydroxyacid synthase (AHAS) confer whole-plant resistance and may reduce plant fitness. This study was done to determine the impact of different watering and temperature regimes on the germination, growth, and seed production of eastern black nightshade populations resistant (R) to AHAS inhibitors as conferred by an Ala205Val substitution in their AHAS. Growth and reproductive ability of four R and four susceptible (S) populations were determined in growth-cabinet and greenhouse studies. The R populations had lower total berry and viable seed production per plant than S under optimal conditions because of slower berry maturation. Seed production of both S and R populations decreased under lower or higher than optimal watering regimes; however, this reduction was more pronounced for the S populations so that seed production was comparable across S and R. The R populations had significantly higher germination and vegetative growth under cooler alternating temperature regimes. Although there were no differences between R and S plants under stress conditions, under optimal growth conditions, the Ala205Val substitution comes at a significant cost in eastern black nightshade. Under optimal growth conditions and in the absence of herbicide selection, S populations should eventually dominate over R; however, the lack of fitness differences under stress conditions could enhance the persistence of the R individuals.

scholarly journals An antibiotic-sensing leader peptide regulates translation and premature Rho-dependent transcription termination of thetopAIgene inEscherichia coli

2019 ◽  
Author(s):  
Gabriele Baniulyte ◽  
Joseph T. Wade
Keyword(s):  
Conformational Changes ◽  
Rna Structure ◽  
Transcription Termination ◽  
Regulatory Elements ◽  
Growth Conditions ◽  
Translational Repression ◽  
Leader Peptide ◽  
Rna Structures ◽  
Ribosome Stalling ◽  
Specific Manner

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.

scholarly journals Rpb4p, a Subunit of RNA Polymerase II, Mediates mRNA Export during Stress

2003 ◽  
Vol 14 (7) ◽  
pp. 2744-2755 ◽  
Author(s):  
Marganit Farago ◽  
Tal Nahari ◽  
Christopher Hammel ◽  
Charles N. Cole ◽  
Mordechai Choder
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mrna Export ◽  
Optimal Growth ◽  
Cellular Responses ◽  
Growth Conditions ◽  
Stress Conditions ◽  
Major Mechanism ◽  
A Subunit

Changes in gene expression represent a major mechanism by which cells respond to stress. We and other investigators have previously shown that the yeast RNA polymerase II subunit Rpb4p is required for transcription under various stress conditions, but not under optimal growth conditions. Here we show that, in addition to its role in transcription, Rpb4p is also required for mRNA export, but only when cells are exposed to stress conditions. The roles of Rpb4p in transcription and in mRNA export can be uncoupled genetically by specific mutations in Rpb4p. Both functions of Rpb4p are required to maintain cell viability during stress. We propose that Rpb4p participates in the cellular responses to stress at the interface of the transcription and the export machineries.

scholarly journals Translation of a leaderless reporter is robust during exponential growth and well sustained during stress conditions in Mycobacterium tuberculosis

2021 ◽  
Author(s):  
A. D. Grabowska ◽  
N. Andreu ◽  
T. Cortes
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Stress Conditions ◽  
Shine Dalgarno Sequence ◽  
Overall Ratio

Abstract Mycobacterium tuberculosis expresses a large number of leaderless mRNA transcripts; these lack the 5’ leader region, which usually contains the Shine-Dalgarno sequence required for translation initiation in bacteria. In M. tuberculosis, transcripts encoding proteins with secondary adaptive functions are predominantly leaderless and the overall ratio of leaderless to Shine-Dalgarno transcripts significantly increases during growth arrest, suggesting that leaderless translation might be important during persistence in the host. However, whether these two types of transcripts are translated with differing efficiencies during stress conditions that induce growth arrest and during optimal growth conditions, is unclear. Here, using bioluminescent reporter strains, we detect robust leaderless translation during exponential in vitro growth and we show that leaderless translation is more stable than Shine-Dalgarno translation during adaptation to stress conditions. Upon entrance into nutrient starvation and after nitric oxide exposure, leaderless translation is significantly less affected by the stress than Shine-Dalgarno translation. Similarly, during the early stages of infection of macrophages, the levels of leaderless translation are more stable than those of Shine-Dalgarno translation. These results suggest that leaderless translation may offer an advantage in the physiology of M. tuberculosis. Identification of the molecular mechanisms underlying this translational regulation may provide insights into persistent infection.

scholarly journals Translation of a Leaderless Reporter Is Robust During Exponential Growth and Well Sustained During Stress Conditions in Mycobacterium tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna D. Grabowska ◽  
Nuria Andreu ◽  
Teresa Cortes
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Stress Conditions ◽  
Pcr Analysis ◽  
Shine Dalgarno Sequence

Mycobacterium tuberculosis expresses a large number of leaderless mRNA transcripts; these lack the 5′ leader region, which usually contains the Shine–Dalgarno sequence required for translation initiation in bacteria. In M. tuberculosis, transcripts encoding proteins like toxin–antitoxin systems are predominantly leaderless and the overall ratio of leaderless to Shine–Dalgarno transcripts significantly increases during growth arrest, suggesting that leaderless translation might be important during persistence in the host. However, whether these two types of transcripts are translated with differing efficiencies during optimal growth conditions and during stress conditions that induce growth arrest, is unclear. Here, we have used the desA1 (Rv0824c) and desA2 (Rv1094) gene pair as representative for Shine–Dalgarno and leaderless transcripts in M. tuberculosis respectively; and used them to construct bioluminescent reporter strains. We detect robust leaderless translation during exponential in vitro growth, and we show that leaderless translation is more stable than Shine–Dalgarno translation during adaptation to stress conditions. These changes are independent from transcription, as transcription levels did not significantly change following quantitative real-time PCR analysis. Upon entrance into nutrient starvation and after nitric oxide exposure, leaderless translation is significantly less affected by the stress than Shine–Dalgarno translation. Similarly, during the early stages of infection of macrophages, the levels of leaderless translation are transiently more stable than those of Shine–Dalgarno translation. These results suggest that leaderless translation may offer an advantage in the physiology of M. tuberculosis. Identification of the molecular mechanisms underlying this translational regulation may provide insights into persistent infection.

scholarly journals Consequences of a Deletion in dspA on Transcript Accumulation in Synechocystis sp. Strain PCC6803

2004 ◽  
Vol 186 (12) ◽  
pp. 3889-3902 ◽  
Author(s):  
Chao-Jung Tu ◽  
Jeffrey Shrager ◽  
Robert L. Burnap ◽  
Bradley L. Postier ◽  
Arthur R. Grossman
Keyword(s):  
Gene Expression ◽  
Light Exposure ◽  
Optimal Growth ◽  
Growth Conditions ◽  
High Light ◽  
Stress Conditions ◽  
Light Conditions ◽  
Wild Type ◽  
Transcript Accumulation ◽  
Low Light

ABSTRACT A sensor histidine kinase of Synechococcus sp. strain PCC7942, designated nblS, was previously identified and shown to be critical for the acclimation of cells to high-light and nutrient limitation conditions and to influence the expression of a number of light-responsive genes. The nblS orthologue in Synechocystis sp. strain PCC6803 is designated dspA (also called hik33). We have generated a dspA null mutant and analyzed global gene expression in both the mutant and wild-type strains under high- and low-light conditions. The mutant is aberrant for the expression of many genes encoding proteins critical for photosynthesis, phosphate and carbon acquisition, and the amelioration of stress conditions. Furthermore, transcripts from a number of genes normally detected only during exposure of wild-type cells to high-light conditions become partially constitutive in the low-light-grown dspA mutant. Other genes for which transcripts decline upon exposure of wild-type cells to high light are already lower in the mutant during growth in low light. These results suggest that DspA may influence gene expression in both a positive and a negative manner and that the dspA mutant behaves as if it were experiencing stress conditions (e.g., high-light exposure) even when maintained at near-optimal growth conditions for wild-type cells. This is discussed with respect to the importance of DspA for regulating the responses of the cell to environmental cues.

scholarly journals Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

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.

scholarly journals Isolation of a gene required for programmed initiation of development by Aspergillus nidulans.

1992 ◽  
Vol 12 (9) ◽  
pp. 3827-3833 ◽  
Author(s):  
T H Adams ◽  
W A Hide ◽  
L N Yager ◽  
B N Lee
Keyword(s):  
Life Cycle ◽  
Aspergillus Nidulans ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Nutrient Deprivation ◽  
Deletion Mutants ◽  
Wild Type ◽  
Microbial Development ◽  
Type Strains ◽  
Posttranscriptional Level

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.

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