translational activity
Recently Published Documents


TOTAL DOCUMENTS

209
(FIVE YEARS 65)

H-INDEX

30
(FIVE YEARS 5)

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Gabriel Therizols ◽  
Zeina Bash-Imam ◽  
Baptiste Panthu ◽  
Christelle Machon ◽  
Anne Vincent ◽  
...  

AbstractMechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5′-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes.


2022 ◽  
Author(s):  
Jessica T. Stieglitz ◽  
Priyanka Lahiri ◽  
Matthew I. Stout ◽  
James A. Van Deventer

Archaeal pyrrolysyl-tRNA synthetases (PylRSs) have been used to genetically encode over 200 distinct noncanonical amino acids (ncAAs) in proteins in E. coli and mammalian cells. This vastly expands the range of chemical functionality accessible within proteins produced in these organisms. Despite these clear successes, explorations of PylRS function in yeast remains limited. In this work, we demonstrate that the Methanomethylophilus alvus PylRS (MaPylRS) and its cognate tRNACUA support the incorporation of ncAAs into proteins produced in S. cerevisiae using stop codon suppression methodologies. Additionally, we prepared three MaPylRS mutants originally engineered in E. coli and determined that all three were translationally active with one or more ncAAs, although with low efficiencies of ncAA incorporation in comparison to the parent MaPylRS. Alongside MaPylRS variants, we evaluated the translational activity of previously reported Methanosarcina mazei, Methanosarcina barkeri, and chimeric M. mazei and M. barkeri PylRSs. Using the yeast strain RJY100, and pairing these aaRSs with the M. barkeri tRNACUA, we did not observe any detectable stop codon suppression activity under the same conditions that produced moderately efficient ncAA incorporation with MaPylRS. The addition of MaPylRS to the orthogonal translation machinery toolkit in yeast potentially opens the door to hundreds of ncAAs that have not previously been genetically encodable using other aminoacyl-tRNA synthetase/tRNA pairs. Extending the scope of ncAA incorporation in yeast could powerfully advance chemical and biological research for applications ranging from basic biological discovery to enzyme engineering and therapeutic protein lead discovery.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Jiao Wei ◽  
Aimin Hui

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine’s efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus’ genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.


2021 ◽  
Vol 12 ◽  
Author(s):  
Manfred Anim ◽  
Georgios Sogkas ◽  
Gunnar Schmidt ◽  
Natalia Dubrowinskaja ◽  
Torsten Witte ◽  
...  

NF-κB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). NFKB1 encodes for the p105 precursor protein of NF-κB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic NFKB1 variants have been shown to cause (haplo) insufficiency. Our report describes a novel NFKB1 missense variant (c.691C>T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C>T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NFκB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers.


2021 ◽  
Vol 10 (1) ◽  
pp. 33
Author(s):  
Yasushi Maki ◽  
Hideji Yoshida

Bacteria convert active 70S ribosomes to inactive 100S ribosomes to survive under various stress conditions. This state, in which the ribosome loses its translational activity, is known as ribosomal hibernation. In gammaproteobacteria such as Escherichia coli, ribosome modulation factor and hibernation-promoting factor are involved in forming 100S ribosomes. The expression of ribosome modulation factor is regulated by (p)ppGpp (which is induced by amino acid starvation), cAMP-CRP (which is stimulated by reduced metabolic energy), and transcription factors involved in biofilm formation. This indicates that the formation of 100S ribosomes is an important strategy for bacterial survival under various stress conditions. In recent years, the structures of 100S ribosomes from various bacteria have been reported, enhancing our understanding of the 100S ribosome. Here, we present previous findings on the 100S ribosome and related proteins and describe the stress-response pathways involved in ribosomal hibernation.


2021 ◽  
Author(s):  
◽  
Sally-Ann Spencer

<p>This thesis examines discourses and practices surrounding German-English translated books in the contemporary German and Anglo-American contexts, focusing on works published as trade fiction. It thereby provides the chronological extension to an existing line of studies that evaluate the production and reception of German-English literary translations in the second half of the twentieth century: notably, the survey volumes by Uta Kreuter (1985), Mark Rectanus (1990a) and, more recently, Wiebke Sievers (2007) who concludes her assessment period in 1999.Continuing the investigation into the twenty-first century, the present thesis combines research into new developments in selected focal territories – Germany, the UK and US – with an enquiry into the contemporary relevance of political and other borders in the circulation of German-English translated books. It thus offers an up-to-date account of activities for German-English translation in these territories; at the same time, it contributes to sociologically oriented scholarship on a methodological and theoretical level.  The period under consideration is notable in two key respects. First, it coincides with technological innovations that are transforming the book business and calling into question existing communications paradigms (Bhaskar 2013). Assessing the impact of these innovations, the thesis examines changing licensing, publishing and retail practices for German-English translated books and evaluates the role of institutional and other frameworks in the circulation of literary products and texts. Second, activities for the translation of literature in the UK and US have proliferated since the early 2000s, indicating a need to move beyond Lawrence Venuti’s diagnosis of an Anglo-American disregard for translated literature (1995), which provides the backdrop for Sievers’s account of German-English translation in the UK (2007). Accordingly, the thesis considers German-English translated books in the context of this upsurge in projects to celebrate translation in the UK and US, and explores the intersection of activities for translation into English with programmes sponsored by intermediaries in Germany to promote the translation of German-language works.  The advancement of the thesis through the ‘macro, mezzo and micro’ levels of analysis serves, on the one hand, to illuminate different aspects of German-English literary translation and, on the other, to interrogate models for sociological translation research (Sapiro 2008). The investigation begins with an analysis of accounts of global translation production, revealing deficiencies in proposed mappings of translational activity and highlighting the deployment of statistical data on book translation for polemical or promotional ends. Drawing on original fieldwork and primary sources, it then considers publishing practices and support programmes for German-English translation in the UK and US, and examines the translational fortunes of selected German-language books and their UK and US editions, thereby connecting with current scholarship on the Anglo-American book business (Thompson 2012) and with research in German Studies associated with the ‘transnational’ paradigm (Taberner 2011a).</p>


2021 ◽  
Author(s):  
◽  
Sally-Ann Spencer

<p>This thesis examines discourses and practices surrounding German-English translated books in the contemporary German and Anglo-American contexts, focusing on works published as trade fiction. It thereby provides the chronological extension to an existing line of studies that evaluate the production and reception of German-English literary translations in the second half of the twentieth century: notably, the survey volumes by Uta Kreuter (1985), Mark Rectanus (1990a) and, more recently, Wiebke Sievers (2007) who concludes her assessment period in 1999.Continuing the investigation into the twenty-first century, the present thesis combines research into new developments in selected focal territories – Germany, the UK and US – with an enquiry into the contemporary relevance of political and other borders in the circulation of German-English translated books. It thus offers an up-to-date account of activities for German-English translation in these territories; at the same time, it contributes to sociologically oriented scholarship on a methodological and theoretical level.  The period under consideration is notable in two key respects. First, it coincides with technological innovations that are transforming the book business and calling into question existing communications paradigms (Bhaskar 2013). Assessing the impact of these innovations, the thesis examines changing licensing, publishing and retail practices for German-English translated books and evaluates the role of institutional and other frameworks in the circulation of literary products and texts. Second, activities for the translation of literature in the UK and US have proliferated since the early 2000s, indicating a need to move beyond Lawrence Venuti’s diagnosis of an Anglo-American disregard for translated literature (1995), which provides the backdrop for Sievers’s account of German-English translation in the UK (2007). Accordingly, the thesis considers German-English translated books in the context of this upsurge in projects to celebrate translation in the UK and US, and explores the intersection of activities for translation into English with programmes sponsored by intermediaries in Germany to promote the translation of German-language works.  The advancement of the thesis through the ‘macro, mezzo and micro’ levels of analysis serves, on the one hand, to illuminate different aspects of German-English literary translation and, on the other, to interrogate models for sociological translation research (Sapiro 2008). The investigation begins with an analysis of accounts of global translation production, revealing deficiencies in proposed mappings of translational activity and highlighting the deployment of statistical data on book translation for polemical or promotional ends. Drawing on original fieldwork and primary sources, it then considers publishing practices and support programmes for German-English translation in the UK and US, and examines the translational fortunes of selected German-language books and their UK and US editions, thereby connecting with current scholarship on the Anglo-American book business (Thompson 2012) and with research in German Studies associated with the ‘transnational’ paradigm (Taberner 2011a).</p>


Plants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2672
Author(s):  
Shimeng Tan ◽  
Yanying Chen ◽  
Guoying Zhou ◽  
Junang Liu

Anthracnose, caused by Colletotrichum spp., is a significant disease affecting oil tea (Camellia oleifera Abel.). Extensive molecular studies have demonstrated that Colletotrichum fructicola is the dominant pathogen of oil tea anthracnose in China. This study aims to investigate differences in molecular processes and regulatory genes at a late stage of infection of C. fructicola, to aid in understanding differences in pathogenic mechanisms of C. fructicola of different geographic populations. We compared the pathogenicity of C. fructicola from different populations (Wuzhishan, Hainan province, and Shaoyang, Hunan province) and gene expression of representative strains of the two populations before and after inoculation in oil tea using RNA sequencing. The results revealed that C. fructicola from Wuzhishan has a more vital ability to impact oil tea leaf tissue. Following infection with oil tea leaves, up-regulated genes in the strains from two geographic populations were associated with galactosidase activity, glutamine family amino acid metabolism, arginine, and proline metabolism. Additionally, up-regulated gene lists associated with infection by Wuzhishan strains were significantly enriched in purine metabolism pathways, while Shaoyang strains were not. These results indicate that more transcriptional and translational activity and the greater regulation of the purine metabolism pathway in the C. fructicola of the Wuzhishan strain might contribute to its stronger pathogenicity.


Author(s):  
Nadja Capus ◽  
Ivana Havelka

AbstractLegal wiretapping has gained importance in law enforcement along with the development of information and communication technology. Understanding the language of intercepted persons is essential for the success of a police investigation. Hence, intercept interpreters, as we suggest calling them in this article, are hired. Little is known about this specific work at the interface between language and law. With this article, we desire to contribute to closing this gap by focussing particularly on the translational activity. Our study identifies a fragmented field of research due to the difficulty in accessing workers in this specific field who interpret in a highly confidential phase of criminal investigations. The findings, which are drawn from scarce studies and our empirical data derived from an online questionnaire for a pilot study in Switzerland, demonstrate the wide range of the performed activity intercept interpreting. This article is the first to present translational activity from the perspective of intercept interpreters. The activity differs in many ways from interpretation in court hearings or police interviews. Hence, we suggest categorising interlingual intercept interpretation as a translational activity sui generis and—since previous research has not done justice to the ethical and deontological questions that intercept interpretation raises—advocate for further transdisciplinary research in this field of translation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sithumini M. W. Lokupathirage ◽  
Yoshimi Tsuda ◽  
Kodai Ikegame ◽  
Kisho Noda ◽  
Devinda S. Muthusinghe ◽  
...  

AbstractSevere fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes novel zoonotic diseases in Asian countries including China, Japan, South Korea, and Vietnam. In phleboviruses, viral proteins play a critical role in viral particle formation inside the host cells. Viral glycoproteins (GPs) and RNA-dependent RNA polymerase (RdRp) are colocalized in the Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The nucleocapsid (N) protein was widely expressed in the cytoplasm, even in cells coexpressing GP. However, the role of SFTSV N protein remains unclear. The subcellular localization of SFTSV structural proteins was investigated using a confocal microscope. Subsequently, minigenome and immunoprecipitation assays were carried out. The N protein interacts with viral RNA (vRNA) and further shows translational activity with RdRp which is L protein and localized in the ERGIC and Golgi apparatus when co-expressed with GP. On the other hand, mutant N protein did not interact with vRNA either localized in the ERGIC or Golgi apparatus. The interaction between the N protein of SFTSV and vRNA is important for the localization of viral proteins and viral assembly. This study provides useful insights into the life cycle of SFTSV, which will lead to the detection of antiviral targets.


Sign in / Sign up

Export Citation Format

Share Document