Yeast mRNA localization: protein asymmetry, organelle localization and response to stress

2014 ◽  
Vol 42 (4) ◽  
pp. 1256-1260 ◽  
Author(s):  
Mariavittoria Pizzinga ◽  
Mark P. Ashe
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Mrna Localization ◽  
Translational Repression ◽  
Yeast Saccharomyces Cerevisiae ◽  
Processing Bodies ◽  
Control Of Gene Expression ◽  
P Bodies ◽  
Response To Stress ◽  
Kinetics Of

The localization of mRNA forms a key facet of the post-transcriptional control of gene expression and recent evidence suggests that it may be considerably more widespread than previously anticipated. For example, defined mRNA-containing granules can be associated with translational repression or activation. Furthermore, mRNA P-bodies (processing bodies) harbour much of the mRNA decay machinery and stress granules are thought to play a role in mRNA storage. In the present review, we explore the process of mRNA localization in the yeast Saccharomyces cerevisiae, examining connections between organellar mRNA localization and the response to stress. We also review recent data suggesting that even where there is a global relocalization of mRNA, the specificity and kinetics of this process can be regulated.

Pat1 proteins: a life in translation, translation repression and mRNA decay

2010 ◽  
Vol 38 (6) ◽  
pp. 1602-1607 ◽  
Author(s):  
Aline Marnef ◽  
Nancy Standart
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Mrna Decay ◽  
Current Knowledge ◽  
Translational Repression ◽  
Processing Bodies ◽  
P Bodies ◽  
Expression Control ◽  
Gene Expression Control ◽  
Sequential Binding

Pat1 proteins are conserved across eukaryotes. Vertebrates have evolved two Pat1 proteins paralogues, whereas invertebrates and yeast only possess one such protein. Despite their lack of known domains or motifs, Pat1 proteins are involved in several key post-transcriptional mechanisms of gene expression control. In yeast, Pat1p interacts with translating mRNPs (messenger ribonucleoproteins), and is responsible for translational repression and decapping activation, ultimately leading to mRNP degradation. Drosophila HPat and human Pat1b (PatL1) proteins also have conserved roles in the 5′→3′ mRNA decay pathway. Consistent with their functions in silencing gene expression, Pat1 proteins localize to P-bodies (processing bodies) in yeast, Drosophila, Caenorhabditis elegans and human cells. Altogether, Pat1 proteins may act as scaffold proteins allowing the sequential binding of repression and decay factors on mRNPs, eventually leading to their degradation. In the present mini-review, we present the current knowledge on Pat1 proteins in the context of their multiple functions in post-transcriptional control.

scholarly journals Mammalian GW220/TNGW1 is essential for the formation of GW/P bodies containing miRISC

2012 ◽  
Vol 198 (4) ◽  
pp. 529-544 ◽  
Author(s):  
Virginia Castilla-Llorente ◽  
Lee Spraggon ◽  
Miwako Okamura ◽  
Saif Naseeruddin ◽  
Matthew Adamow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Cellular Localization ◽  
Translational Repression ◽  
P Bodies ◽  
Target Mrna ◽  
Core Components ◽  
Mirna Pathway

The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.

scholarly journals Defects in the Secretory Pathway and High Ca2+ Induce Multiple P-bodies

2010 ◽  
Vol 21 (15) ◽  
pp. 2624-2638 ◽  
Author(s):  
Cornelia Kilchert ◽  
Julie Weidner ◽  
Cristina Prescianotto-Baschong ◽  
Anne Spang
Keyword(s):  
Osmotic Stress ◽  
Secretory Pathway ◽  
Small Gtpase ◽  
Processing Bodies ◽  
P Bodies ◽  
Intracellular Signals ◽  
Intracellular Ca ◽  
Response To Stress ◽  
Cellular Stresses ◽  
Translational Block

mRNA is sequestered and turned over in cytoplasmic processing bodies (PBs), which are induced by various cellular stresses. Unexpectedly, in Saccharomyces cerevisiae, mutants of the small GTPase Arf1 and various secretory pathway mutants induced a significant increase in PB number, compared with PB induction by starvation or oxidative stress. Exposure of wild-type cells to osmotic stress or high extracellular Ca2+ mimicked this increase in PB number. Conversely, intracellular Ca2+-depletion strongly reduced PB formation in the secretory mutants. In contrast to PB induction through starvation or osmotic stress, PB formation in secretory mutants and by Ca2+ required the PB components Pat1 and Scd6, and calmodulin, indicating that different stressors act through distinct pathways. Consistent with this hypothesis, when stresses were combined, PB number did not correlate with the strength of the translational block, but rather with the type of stress encountered. Interestingly, independent of the stressor, PBs appear as spheres of ∼40–100 nm connected to the endoplasmic reticulum (ER), consistent with the idea that translation and silencing/degradation occur in a spatially coordinated manner at the ER. We propose that PB assembly in response to stress occurs at the ER and depends on intracellular signals that regulate PB number.

scholarly journals Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sarah L. Gillen ◽  
Chiara Giacomelli ◽  
Kelly Hodge ◽  
Sara Zanivan ◽  
Martin Bushell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Mrna Stability ◽  
Mrna Localization ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Control Of Gene Expression ◽  
Mrna Fate

Abstract Background Regulation of protein output at the level of translation allows for a rapid adaptation to dynamic changes to the cell’s requirements. This precise control of gene expression is achieved by complex and interlinked biochemical processes that modulate both the protein synthesis rate and stability of each individual mRNA. A major factor coordinating this regulation is the Ccr4-Not complex. Despite playing a role in most stages of the mRNA life cycle, no attempt has been made to take a global integrated view of how the Ccr4-Not complex affects gene expression. Results This study has taken a comprehensive approach to investigate post-transcriptional regulation mediated by the Ccr4-Not complex assessing steady-state mRNA levels, ribosome position, mRNA stability, and protein production transcriptome-wide. Depletion of the scaffold protein CNOT1 results in a global upregulation of mRNA stability and the preferential stabilization of mRNAs enriched for G/C-ending codons. We also uncover that mRNAs targeted to the ER for their translation have reduced translational efficiency when CNOT1 is depleted, specifically downstream of the signal sequence cleavage site. In contrast, translationally upregulated mRNAs are normally localized in p-bodies, contain disorder-promoting amino acids, and encode nuclear localized proteins. Finally, we identify ribosome pause sites that are resolved or induced by the depletion of CNOT1. Conclusions We define the key mRNA features that determine how the human Ccr4-Not complex differentially regulates mRNA fate and protein synthesis through a mechanism linked to codon composition, amino acid usage, and mRNA localization.

scholarly journals The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Small Rnas ◽  
Transcriptional Control ◽  
Cold Shock ◽  
Control Of Gene Expression ◽  
Rna Biology ◽  
Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

scholarly journals Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

2019 ◽  
Vol 20 (12) ◽  
pp. 3073 ◽  
Author(s):  
Ana Dienstbier ◽  
Fabian Amman ◽  
Daniel Štipl ◽  
Denisa Petráčková ◽  
Branislav Večerek
Keyword(s):  
Gene Expression ◽  
Bordetella Pertussis ◽  
Transcriptional Control ◽  
Whooping Cough ◽  
Expression Profiles ◽  
Bacterial Pathogen ◽  
Gene Expression Profiles ◽  
Control Of Gene Expression ◽  
Proteomic Data

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.

scholarly journals Regulatory signals in messenger RNA: determinants of nutrient–gene interaction and metabolic compartmentation

1998 ◽  
Vol 80 (4) ◽  
pp. 307-321
Author(s):  
John E. Hesketh ◽  
M. Helena Vasconcelos ◽  
Giovanna Bermano
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Transcriptional Control ◽  
Regulation Of Gene Expression ◽  
Untranslated Regions ◽  
Nutritional Requirements ◽  
Control Of Gene Expression ◽  
Metabolic Compartmentation ◽  
Post Transcriptional Regulation

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.

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