Regulation of translation is essential for the diverse biological processes involved in development. Particularly, mammalian oocyte development requires the precisely controlled translation of maternal transcripts to coordinate meiotic and early embryo progression while transcription is silent. It has been recently reported that key components of mRNA translation control are short and long noncoding RNAs (ncRNAs). We found that the ncRNABrain cytoplasmic 1 (BC1) has a role in the fully grown germinal vesicle (GV) mouse oocyte, where is highly expressed in the cytoplasm associated with polysomes. Overexpression of BC1 in GV oocyte leads to a minute decrease in global translation with a significant reduction of specific mRNA translation via interaction with the Fragile X Mental Retardation Protein (FMRP). BC1 performs a repressive role in translation only in the GV stage oocyte without forming FMRP or Poly(A) granules. In conclusion, BC1 acts as the translational repressor of specific mRNAs in the GV stage via its binding to a subset of mRNAs and physical interaction with FMRP. The results reported herein contribute to the understanding of the molecular mechanisms of developmental events connected with maternal mRNA translation.

• Klíčová slova
• Non-coding RNA, development, embryo, oocyte, translation,
• MeSH
• cytoplazma genetika   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nekódující RNA genetika   MeSH
• oocyty cytologie   fyziologie   MeSH
• oogeneze * MeSH
• polyribozomy genetika   metabolismus   MeSH
• proteosyntéza * MeSH
• RNA malá cytoplazmatická genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nekódující RNA MeSH
• RNA malá cytoplazmatická MeSH

OBJECTIVE: We investigate machine translation (MT) of user search queries in the context of cross-lingual information retrieval (IR) in the medical domain. The main focus is on techniques to adapt MT to increase translation quality; however, we also explore MT adaptation to improve effectiveness of cross-lingual IR. METHODS AND DATA: Our MT system is Moses, a state-of-the-art phrase-based statistical machine translation system. The IR system is based on the BM25 retrieval model implemented in the Lucene search engine. The MT techniques employed in this work include in-domain training and tuning, intelligent training data selection, optimization of phrase table configuration, compound splitting, and exploiting synonyms as translation variants. The IR methods include morphological normalization and using multiple translation variants for query expansion. The experiments are performed and thoroughly evaluated on three language pairs: Czech-English, German-English, and French-English. MT quality is evaluated on data sets created within the Khresmoi project and IR effectiveness is tested on the CLEF eHealth 2013 data sets. RESULTS: The search query translation results achieved in our experiments are outstanding - our systems outperform not only our strong baselines, but also Google Translate and Microsoft Bing Translator in direct comparison carried out on all the language pairs. The baseline BLEU scores increased from 26.59 to 41.45 for Czech-English, from 23.03 to 40.82 for German-English, and from 32.67 to 40.82 for French-English. This is a 55% improvement on average. In terms of the IR performance on this particular test collection, a significant improvement over the baseline is achieved only for French-English. For Czech-English and German-English, the increased MT quality does not lead to better IR results. CONCLUSIONS: Most of the MT techniques employed in our experiments improve MT of medical search queries. Especially the intelligent training data selection proves to be very successful for domain adaptation of MT. Certain improvements are also obtained from German compound splitting on the source language side. Translation quality, however, does not appear to correlate with the IR performance - better translation does not necessarily yield better retrieval. We discuss in detail the contribution of the individual techniques and state-of-the-art features and provide future research directions.

• Klíčová slova
• Compound splitting, Cross-language information retrieval, Domain adaptation of statistical machine translation, Intelligent training data selection for machine translation, Medical query translation, Statistical machine translation,
• MeSH
• algoritmy MeSH
• jazyk (prostředek komunikace) MeSH
• překládání * MeSH
• software MeSH
• ukládání a vyhledávání informací metody   MeSH
• umělá inteligence MeSH
• Unified Medical Language System MeSH
• zpracování přirozeného jazyka MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OTUD1 is a deubiquitinating enzyme involved in many cellular processes including cancer and innate, immune signaling pathways. Here, we perform a proximity labeling-based interactome study that identifies OTUD1 largely present in the translation and RNA metabolism protein complexes. Biochemical analysis validates OTUD1 association with ribosome subunits, elongation factors and the E3 ubiquitin ligase ZNF598 but not with the translation initiation machinery. OTUD1 catalytic activity suppresses polyA triggered ribosome stalling through inhibition of ZNF598-mediated RPS10 ubiquitination and stimulates formation of polysomes. Finally, analysis of gene expression suggests that OTUD1 regulates the stability of rare codon rich mRNAs by antagonizing ZNF598.

• Klíčová slova
• ribosome stalling, translation, ubiquitination,
• MeSH
• deubikvitinasy genetika   metabolismus   MeSH
• kodon MeSH
• messenger RNA genetika   metabolismus   MeSH
• poly A * metabolismus   MeSH
• proteosyntéza MeSH
• transportní proteiny * metabolismus   MeSH
• ubikvitinace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• deubikvitinasy MeSH
• kodon MeSH
• messenger RNA MeSH
• poly A * MeSH
• transportní proteiny * MeSH

Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in translation termination in vivo. A substantial proportion of eIF3, HCR1 and eukaryotic release factor 3 (eRF3) but not eIF5 (a well-defined "initiation-specific" binding partner of eIF3) specifically co-sediments with 80S couples isolated from RNase-treated heavy polysomes in an eRF1-dependent manner, indicating the presence of eIF3 and HCR1 on terminating ribosomes. eIF3 and HCR1 also occur in ribosome- and RNA-free complexes with both eRFs and the recycling factor ABCE1/RLI1. Several eIF3 mutations reduce rates of stop codon read-through and genetically interact with mutant eRFs. In contrast, a slow growing deletion of hcr1 increases read-through and accumulates eRF3 in heavy polysomes in a manner suppressible by overexpressed ABCE1/RLI1. Based on these and other findings we propose that upon stop codon recognition, HCR1 promotes eRF3·GDP ejection from the post-termination complexes to allow binding of its interacting partner ABCE1/RLI1. Furthermore, the fact that high dosage of ABCE1/RLI1 fully suppresses the slow growth phenotype of hcr1Δ as well as its termination but not initiation defects implies that the termination function of HCR1 is more critical for optimal proliferation than its function in translation initiation. Based on these and other observations we suggest that the assignment of HCR1 as a bona fide eIF3 subunit should be reconsidered. Together our work characterizes novel roles of eIF3 and HCR1 in stop codon recognition, defining a communication bridge between the initiation and termination/recycling phases of translation.

• MeSH
• ABC transportéry genetika   MeSH
• eukaryotický iniciační faktor 3 genetika   MeSH
• iniciační faktory genetika   MeSH
• mutace MeSH
• proteosyntéza * MeSH
• Saccharomyces cerevisiae - proteiny genetika   MeSH
• Saccharomyces cerevisiae genetika   MeSH
• sekvence aminokyselin MeSH
• terminace translace peptidového řetězce * MeSH
• terminační kodon genetika   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• eukaryotický iniciační faktor 3 MeSH
• HCR1 protein, S cerevisiae MeSH Prohlížeč
• iniciační faktory MeSH
• RLI1 protein, S cerevisiae MeSH Prohlížeč
• Saccharomyces cerevisiae - proteiny MeSH
• terminační kodon MeSH

The last forty years of molecular biology and biochemistry were enormously rich in discoveries, which were not foreseen even by the most eminent scientists of that time. The findings of 1993-2000 profoundly enlarged our views on translation termination, clearly showing that our previous understanding was enormously oversimplified. Now the structural basis is created for much better insight into functions of termination factors. The story of translation termination in eukaryotes could be taken as an illustration of a general trend of molecular biology: "From simplicity to complexity". However, genuine knowledge requires that after this stage a third phase has to be reached, which is "From complexity to clarity". This has not yet been achieved in translation termination and therefore makes this topic quite attractive for researchers.

• MeSH
• eukaryotické buňky MeSH
• proteosyntéza * MeSH
• umlčování genů * MeSH
• Publikační typ
• úvodníky MeSH

A hallmark of oocyte development in mammals is the dependence on the translation and utilization of stored RNA and proteins rather than the de novo transcription of genes in order to sustain meiotic progression and early embryo development. In the absence of transcription, the completion of meiosis and early embryo development in mammals relies significantly on maternally synthesized RNAs. Post-transcriptional control of gene expression at the translational level has emerged as an important cellular function in normal development. Therefore, the regulation of gene expression in oocytes is controlled almost exclusively at the level of mRNA and protein stabilization and protein synthesis. This current review is focused on the recently emerged findings on RNA distribution related to the temporal and spatial translational control of the meiotic progression of the mammalian oocyte.

• Klíčová slova
• Meiosis, Oocyte, RNA, RNP, Translation,
• MeSH
• lidé MeSH
• meióza MeSH
• oocyty cytologie   metabolismus   MeSH
• oogeneze MeSH
• proteosyntéza * MeSH
• RNA analýza   genetika   MeSH
• transkriptom MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• RNA MeSH

For many years initiation and termination of mRNA translation have been studied separately. However, a direct link between these 2 isolated stages has been suggested by the fact that some initiation factors also control termination and can even promote ribosome recycling; i.e. the last stage where post-terminating 80S ribosomes are split to start a new round of initiation. Notably, it is now firmly established that, among other factors, ribosomal recycling critically requires the NTPase ABCE1. However, several earlier reports have proposed that ABCE1 also somehow participates in the initiation complex assembly. Based on an extended analysis of our recently published late-stage 48S initiation complex from rabbit, here we provide new mechanistic insights into this putative role of ABCE1 in initiation. This point of view represents the first structural evidence in which the regulatory role of the recycling factor ABCE1 in initiation is discussed and establishes a corner stone for elucidating the interplay between ABCE1 and several initiation factors during the transit from ribosomal recycling to formation of the elongation competent 80S initiation complex.

• Klíčová slova
• ABCE1, cryo-EM, recycling, ribosome, translation,
• MeSH
• ABC transportéry chemie   metabolismus   MeSH
• elongační faktory MeSH
• hydrolýza MeSH
• iniciace translace peptidového řetězce * MeSH
• iniciační faktory metabolismus   MeSH
• králíci MeSH
• molekulární modely MeSH
• nukleosidy chemie   MeSH
• ribozomy metabolismus   MeSH
• terminace translace peptidového řetězce MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• ABC transportéry MeSH
• elongační faktory MeSH
• iniciační faktory MeSH
• nukleosidy MeSH

Regulation of translation represents a critical step in the regulation of gene expression. In plants, the translation regulation plays an important role at all stages of development and, during stress responses, functions as a fast and flexible tool which not only modulates the global translation rate but also controls the production of specific proteins. Regulation of translation is mostly focused on the initiation phase. There, one of essential initiation factors is the large multisubunit protein complex of eukaryotic translation initiation factor 3 (eIF3). In all eukaryotes, the general eIF3 function is to scaffold the formation of the translation initiation complex and to enhance the accuracy of scanning mechanism for start codon selection. Over the past decades, additional eIF3 functions were described as necessary for development in various eukaryotic organisms, including plants. The importance of the eIF3 complex lies not only at the global level of initiation event, but also in the precise translation regulation of specific transcripts. This review gathers the available information on functions of the plant eIF3 complex.

• Klíčová slova
• Plant development, Translation, Translation regulation, Upstream open reading frame (uORF),
• MeSH
• eukaryotický iniciační faktor 3 * metabolismus   MeSH
• kodon iniciační MeSH
• proteosyntéza genetika   MeSH
• regulace genové exprese u rostlin * genetika   MeSH
• rostliny genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• eukaryotický iniciační faktor 3 * MeSH
• kodon iniciační MeSH

Translation accuracy is one of the most critical factors for protein synthesis. It is regulated by the ribosome and its dynamic behavior, along with translation factors that direct ribosome rearrangements to make translation a uniform process. Earlier structural studies of the ribosome complex with arrested translation factors laid the foundation for an understanding of ribosome dynamics and the translation process as such. Recent technological advances in time-resolved and ensemble cryo-EM have made it possible to study translation in real time at high resolution. These methods provided a detailed view of translation in bacteria for all three phases: initiation, elongation, and termination. In this review, we focus on translation factors (in some cases GTP activation) and their ability to monitor and respond to ribosome organization to enable efficient and accurate translation. This article is categorized under: Translation > Ribosome Structure/Function Translation > Mechanisms.

• Klíčová slova
• cryoelectron microscopy, structural biology, translation,
• MeSH
• elektronová kryomikroskopie metody   MeSH
• ribozomy * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Optogenetic tools have revolutionized the study of receptor-mediated processes, but such tools are lacking for RNA-controlled systems. In particular, light-activated regulatory RNAs are needed for spatiotemporal control of gene expression. To fill this gap, we used in vitro selection to isolate a novel riboswitch that selectively binds the trans isoform of a stiff-stilbene (amino-tSS)-a rapidly and reversibly photoisomerizing small molecule. Structural probing revealed that the RNA binds amino-tSS about 100-times stronger than the cis photoisoform (amino-cSS). In vitro and in vivo functional analysis showed that the riboswitch, termed Werewolf-1 (Were-1), inhibits translation of a downstream open reading frame when bound to amino-tSS. Photoisomerization of the ligand with a sub-millisecond pulse of light induced the protein expression. In contrast, amino-cSS supported protein expression, which was inhibited upon photoisomerization to amino-tSS. Reversible photoregulation of gene expression using a genetically encoded RNA will likely facilitate high-resolution spatiotemporal analysis of complex RNA processes.

• Klíčová slova
• E. coli, aptamer, biochemistry, chemical biology, luciferase, photoregulation, riboswitch, stilbene, translation initiation,
• MeSH
• bakteriální RNA genetika   MeSH
• Escherichia coli genetika   MeSH
• messenger RNA metabolismus   MeSH
• proteosyntéza * MeSH
• regulace genové exprese u bakterií MeSH
• riboswitch * MeSH
• spektrální analýza metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• bakteriální RNA MeSH
• messenger RNA MeSH
• riboswitch * MeSH