| 1. |
- Arghiani, Nahid, et al.
(författare)
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Role of microRNAs in COVID-19 with implications for therapeutics
- 2021
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier BV. - 0753-3322 .- 1950-6007. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is a pneumonia-like disease with highly transmittable and pathogenic properties caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects both animals and humans. Although many efforts are currently underway to test possible therapies, there is no specific FDA approved drug against SARS-CoV-2 yet. miRNA-directed gene regulation controls the majority of biological processes. In addition, the development and progression of several human diseases are associated with dysregulation of miRNAs. In this regard, it has been shown that changes in miRNAs are linked to severity of COVID-19 especially in patients with respiratory diseases, diabetes, heart failure or kidney problems. Therefore, targeting these small noncoding-RNAs could potentially alleviate complications from COVID-19. Here, we will review the roles and importance of host and RNA virus encoded miRNAs in COVID-19 pathogenicity and immune response. Then, we focus on potential miRNA therapeutics in the patients who are at increased risk for severe disease.
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| 2. |
- Balagopal, Vidya, et al.
(författare)
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Ways and means of eukaryotic mRNA decay
- 2012
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Ingår i: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. - New York : Elsevier. - 1874-9399. ; 1819:6, s. 593-603
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Forskningsöversikt (refereegranskat)abstract
- Messenger RNA degradation is an important point of control for gene expression. Genome-wide studies on mRNA stability have demonstrated its importance in adaptation and stress response. Most of the key players in mRNA decay appear to have been identified. The study of these proteins brings insight into the mechanism of general and specific targeting of transcripts for degradation. Recruitment and assembly of mRNP complexes enhance and bring specificity to mRNA decay. mRNP complexes can form larger structures that have been found to be ubiquitous in nature. Discovery of P-Bodies, an archetype of this sort of aggregates, has generated interest in the question of where mRNA degrades. This is currently an open question under extensive investigation. This review will discuss in detail the recent developments in the regulation of mRNA decay focusing on yeast as a model system.
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| 3. |
- Brodiazhenko, Tetiana, et al.
(författare)
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Elimination of Ribosome Inactivating Factors Improves the Efficiency of Bacillus subtilis and Saccharomyces cerevisiae Cell-Free Translation Systems
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free translation systems based on cellular lysates optimized for in vitro protein synthesis have multiple applications both in basic and applied science, ranging from studies of translational regulation to cell-free production of proteins and ribosome-nascent chain complexes. In order to achieve both high activity and reproducibility in a translation system, it is essential that the ribosomes in the cellular lysate are enzymatically active. Here we demonstrate that genomic disruption of genes encoding ribosome inactivating factors – HPF in Bacillus subtilis and Stm1 in Saccharomyces cerevisiae – robustly improve the activities of bacterial and yeast translation systems. Importantly, the elimination of B. subtilis HPF results in a complete loss of 100S ribosomes, which otherwise interfere with disome-based approaches for preparation of stalled ribosomal complexes for cryo-electron microscopy studies.
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| 4. |
- Buchan, J Ross, et al.
(författare)
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Analyzing p-bodies and stress granules in Saccharomyces cerevisae
- 2010. - 2
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Ingår i: Guide to yeast genetics. - San Diego : Academic Press. - 9780123751713 - 9780123751720 ; , s. 619-640
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Bokkapitel (refereegranskat)abstract
- Eukaryotic cells contain at least two types of cytoplasmic RNA protein (RNP) granules that contain nontranslating mRNAs. One such RNP granule is a P-body, which contains translationally inactive mRNAs and proteins involved in mRNA degradation and translation repression. A second such RNP granule is a stress granule which also contains mRNAs, some RNA binding proteins and several translation initiation factors, suggesting these granules contain mRNAs stalled in translation initiation. In this chapter, we describe methods to analyze P-bodies and stress granules in Saccharomyces cerevisiae, including procedures to determine if a protein or mRNA can accumulate in either granule, if an environmental perturbation or mutation affects granule size and number, and granule quantification methods.
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| 5. |
- Hu, Anqi, et al.
(författare)
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Reflecting on COVID-19 vaccine hesitancy among South Asian communities in the UK : A learning curve to decolonising the secondary school curriculum
- 2023
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Ingår i: Frontiers in Education. - : Frontiers Media SA. - 2504-284X. ; 8
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Forskningsöversikt (refereegranskat)abstract
- COVID-19 has brought to light the systemic racism faced by ethnic minorities in the UK. During the pandemic, we saw an increase in anti-Asian hate crimes and a lack of support from the government given to both patients and healthcare workers from minority backgrounds on the front lines. This lack of support potentially contributed to the increased susceptibility of ethnic minorities to COVID-19 and also their hesitancy toward the vaccine, particularly the south Asian communities. In this paper we discuss potential reasons for COVID-19 vaccine hesitancy among south Asian groups. Additionally, we propose that introducing a decolonised curriculum in secondary school may enhance cultural awareness with historical context among the white British populations, allowing for more inclusion for south Asian communities. By exploring ways to decolonise specific subjects in the secondary curriculum, this paper aims to set out a guideline for teachers and education professionals on expanding secondary school pupils’ knowledge of racial issues and equality, to start the process of educating a new generation appropriately. We propose that decolonising the secondary school curriculum is a potential long-term solution to eradicating racism and discrimination.
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| 6. |
- Huch, Susanne, 1981-, et al.
(författare)
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An mRNA decapping mutant deficient in P body assembly limits mRNA stabilization in response to osmotic stress
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Yeast is exposed to changing environmental conditions and must adapt its genetic program to provide a homeostatic intracellular environment. An important stress for yeast in the wild is high osmolarity. A key response to this stress is increased mRNA stability primarily by the inhibition of deadenylation. We previously demonstrated that mutations in decapping activators (edc3∆ lsm4∆C), which result in defects in P body assembly, can destabilize mRNA under unstressed conditions. We wished to examine whether mRNA would be destabilized in the edc3∆ lsm4∆C mutant as compared to the wild-type in response to osmotic stress, when P bodies are intense and numerous. Our results show that the edc3∆ lsm4∆C mutant limits the mRNA stability in response to osmotic stress, while the magnitude of stabilization was similar as compared to the wild-type. The reduced mRNA stability in the edc3∆ lsm4∆C mutant was correlated with a shorter PGK1 poly(A) tail. Similarly, the MFA2 mRNA was more rapidly deadenylated as well as significantly stabilized in the ccr4∆ deadenylation mutant in the edc3∆ lsm4∆C background. These results suggest a role for these decapping factors in stabilizing mRNA and may implicate P bodies as sites of reduced mRNA degradation.
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| 7. |
- Huch, Susanne, et al.
(författare)
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Interrelations between translation and general mRNA degradation in yeast
- 2014
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Ingår i: Wiley Interdisciplinary Reviews: RNA. - : John Wiley & Sons. - 1757-7012 .- 1757-7004. ; 5:6, s. 747-763
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Forskningsöversikt (refereegranskat)abstract
- Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system.
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| 8. |
- Huch, Susanne, et al.
(författare)
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Membrane-association of mRNA decapping factors is independent of stress in budding yeast
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence has suggested that the degradation of mRNA occurs on translating ribosomes or alternatively within RNA granules called P bodies, which are aggregates whose core constituents are mRNA decay proteins and RNA. In this study, we examined the mRNA decapping proteins, Dcp1, Dcp2, and Dhh1, using subcellular fractionation. We found that decapping factors co-sediment in the polysome fraction of a sucrose gradient and do not alter their behaviour with stress, inhibition of translation or inhibition of the P body formation. Importantly, their localisation to the polysome fraction is independent of the RNA, suggesting that these factors may be constitutively localised to the polysome. Conversely, polysomal and post-polysomal sedimentation of the decapping proteins was abolished with the addition of a detergent, which shifts the factors to the non-translating RNP fraction and is consistent with membrane association. Using a membrane otation assay, we observed the mRNA decapping factors in the lower density fractions at the buoyant density of membrane-associated proteins. These observations provide further evidence that mRNA decapping factors interact with subcellular membranes, and we suggest a model in which the mRNA decapping factors interact with membranes to facilitate regulation of mRNA degradation.
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| 9. |
- Huch, Susanne, 1981-
(författare)
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Spatial control of mRNA stability in yeast
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The degradation of mRNA is an important modulator of gene expression and the ultimate fate of messenger mRNA. Important steps in the degradation of mRNA include initial shortening of its poly(A) tail followed by the subsequent removal of the m7G cap. These two processes are linked temporally as well as spatially. In addition to physical interactions between proteins involved in these two processes, deadenylation and decapping enzymes and accessory factors are found in P bodies. P bodies are aggregates of protein and mRNA that are induced upon stress in all eukaryotes examined. In this thesis, I examine the spatial localization of decapping factors and explore the role of P bodies in mRNA turnover in the yeast Saccharomyces cerevisiae. This thesis is based on three underlying principles. First, mRNA decapping factors are membrane associated. More so, we show that decapping factors can be co-localized with the endoplasmic reticulum and Golgi apparatus. Second, although P bodies were proposed as sites of mRNA decay, we found that they stabilize mRNA. We examined the role of P bodies in mRNA turnover using a mutant defective in their assembly, edc3∆ lsm4∆C. This strain is mutated in two decapping activators. It combines a deletion of the gene encoding the Edc3 protein and lacks the prion-like domain of Lsm4. Using the edc3∆ lsm4∆C mutant, we demonstrate that mRNA stability is significantly reduced in the absence of P bodies for longer-lived mRNA. The effect of mRNA destabilization was due to increased deadenylation and decapping dependence. Finally, the decapping factor usually found in the cytoplasm, but accumulates in the nucleus in the P body deficient strain (edc3∆ lsm4∆C). This implies a possible role in modulating transcription.A model for the functioning of P bodies that is consistent with our work is that P bodies serve a role as a cytoplasmic sink for degradation factors. By regulating the access of the cytosol to proteins involved in mRNA turnover, P bodies can modulate mRNA stability. This suggests a role for P bodies under stress and their potential importance in stress adaptation.
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| 10. |
- Huch, Susanne, et al.
(författare)
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The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae
- 2016
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Ingår i: Biology Open. - : The company of biologists ltd. - 2046-6390. ; 5:10, s. 1388-1399
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Tidskriftsartikel (refereegranskat)abstract
- The rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC) reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs or alternatively may imply a role for P bodies in mRNA stabilization.
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