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Protein translation

Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
Anne C Conibear, Markus Muttenthaler
The 7th Chemical Protein Synthesis Meeting took place in September 2017 in Haifa, Israel, bringing together 100 scientists from 11 countries. The cutting-edge scientific program included new synthetic strategies and ligation auxiliaries, novel insights into protein signaling and post-translational modifications, and a range of promising therapeutic applications.
March 15, 2018: Cell Chemical Biology
Shannon N Rhoads, Zachary T Monahan, Debra S Yee, Frank P Shewmaker
Subcellular mislocalization and aggregation of the human FUS protein occurs in neurons of patients with subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. FUS is one of several RNA-binding proteins that can functionally self-associate into distinct liquid-phase droplet structures. It is postulated that aberrant interactions within the dense phase-separated state can potentiate FUS's transition into solid prion-like aggregates that cause disease. FUS is post-translationally modified at numerous positions, which affect both its localization and aggregation propensity...
March 16, 2018: International Journal of Molecular Sciences
Andrew R Tee
Mammalian target of rapamycin (mTOR, now referred to as mechanistic target of rapamycin) is considered as the master regulator of cell growth. A definition of cell growth is a build-up of cellular mass through the biosynthesis of macromolecules. mTOR regulation of cell growth and cell size is complex, involving tight regulation of both anabolic and catabolic processes. Upon a growth signal input, mTOR enhances a range of anabolic processes that coordinate the biosynthesis of macromolecules to build cellular biomass, while restricting catabolic processes such as autophagy...
March 16, 2018: International Journal of Molecular Sciences
Renata Gruszka, Magdalena Zakrzewska
The fundamental function of ribonucleic acids is to transfer genetic information from DNA to protein during translation process, however, this is not the only way connecting active RNA sequences with essential biological processes. Up until now, many RNA subclasses of different size, structure, and biological function were identified. Among them, there are non-coding single-stranded microRNAs (miRNAs). This subclass comprises RNAs of 19-25 nucleotides in length that modulate the activity of well-defined coding RNAs and play a crucial role in many physiological and pathological processes...
March 16, 2018: International Journal of Molecular Sciences
Michał Rurek, Magdalena Czołpińska, Tomasz Andrzej Pawłowski, Włodzimierz Krzesiński, Tomasz Spiżewski
Complex proteomic and physiological approaches for studying cold and heat stress responses in plant mitochondria are still limited. Variations in the mitochondrial proteome of cauliflower ( Brassica oleracea var. botrytis ) curds after cold and heat and after stress recovery were assayed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) in relation to mRNA abundance and respiratory parameters. Quantitative analysis of the mitochondrial proteome revealed numerous stress-affected protein spots. In cold, major downregulations in the level of photorespiratory enzymes, porine isoforms, oxidative phosphorylation (OXPHOS) and some low-abundant proteins were observed...
March 16, 2018: International Journal of Molecular Sciences
Zhipeng Zhou, Yunkun Dang, Mian Zhou, Haiyan Yuan, Yi Liu
Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and the abolishment of full-length mRNA...
March 16, 2018: ELife
Valerie Jeanneret, Juan P Ospina, Ariel Diaz, Luis G Manrique, Paola Merino, Laura Gutierrez, Enrique Torre, Fang Wu, Lihong Cheng, Manuel Yepes
Cerebral ischemia causes the presynaptic release of tissue-type plasminogen activator (tPA). The postsynaptic density (PSD) is a postsynaptic structure that provides a matrix where signaling transduction of excitatory synapses takes place. The postsynaptic density protein-95 (PSD-95) is the most abundant scaffolding protein in the postsynaptic density (PSD), where it modulates the postsynaptic response to the presynaptic release of glutamate by regulating the anchoring of glutamate receptors to the PSD. We found that tPA induces the local translation of PSD-95 mRNA and the subsequent recruitment of PSD-95 protein to the PSD, via plasminogen-independent activation of TrkB receptors...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
C Lavanya, Manjunatha M Venkataswamy, M K Sibin, M M Srinivas Bharath, G K Chetan
Increased telomerase activity can be blocked by targeting the hTERT activity at both RNA and catalytic subunits. Various inhibitors had been used to regulate hTERT activity in glioblastoma cell lines and showed promising results. The present study hypothesized that the telomerase specific inhibitor BIBR1532 can effectively down-regulate the telomerase activity in LN18 glioblastoma cell line. LN18 glioblastoma cell line was treated with various concentrations of BIBR1532 at different time intervals. MTT assay was performed to determine cell viability after BIBR1532 treatment...
March 15, 2018: Cytotechnology
Tobias Jung, Matthias Mack
We studied the interaction of the tricarboxylic acid cycle (TCA) enzymes citrate synthase, isocitrate dehydrogenase and malate dehydrogenase in the bacteria Bacillus subtilis and Escherichia coli in vivo. In B. subtilis the genes encoding citrate synthase, isocitrate dehydrogenase and malate dehydrogenase form an operon (citZ-icd-mdh) and predominantly are co-transcribed from a single promoter. In E. coli the corresponding genes gltA, icd and mdh do not form a transcription unit, are scattered around the chromosome and are expressed from different promoters...
March 13, 2018: FEMS Microbiology Letters
Ariel Talavera, Jelle Hendrix, Wim Versées, Dukas Jurėnas, Katleen Van Nerom, Niels Vandenberk, Ranjan Kumar Singh, Albert Konijnenberg, Steven De Gieter, Daniel Castro-Roa, Anders Barth, Henri De Greve, Frank Sobott, Johan Hofkens, Nikolay Zenkin, Remy Loris, Abel Garcia-Pino
Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle...
March 2018: Science Advances
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
Hyangju Kang, Youngmin Park, Yongjik Lee, Yun-Joo Yoo, Inhwan Hwang
Plants represent promising systems for producing various recombinant proteins. One key area of focus for improving this technology is developing methods for producing recombinant proteins at high levels. Many methods have been developed to increase the transcript levels of recombinant genes. However, methods for increasing protein production involving steps downstream of transcription, including translation, have not been fully explored. Here, we investigated the effects of N-glycosylation on protein production and provide evidence that N-glycosylation greatly increases the expression levels of ER-targeted recombinant proteins...
March 15, 2018: Scientific Reports
Venkatraman Ravi, Aditi Jain, Faiz Ahamed, Nowrin Fathma, Perumal Arumugam Desingu, Nagalingam R Sundaresan
Heart is a dynamic organ that undergoes remodeling in response to both physiological and pathological stimuli. One of the fundamental cellular processes that facilitates changes in the size and shape of this muscular organ is the protein synthesis. Traditionally changes in cardiac protein synthesis levels were measured by radiolabeled tracers. However, these methods are often cumbersome and suffer from radioactive risk. Recently a nonradioactive method for detecting protein synthesis under in vitro conditions called the Surface Sensing of Translation (SUnSET) was described in cell lines of mouse dendrites and T cells...
March 15, 2018: Scientific Reports
Ahmet Krasniqi, Matthias D'Huyvetter, Nick Devoogdt, Fredrik Y Frejd, Jens Sorensen, Jens Sorensen, Marleen Keyaerts, Vladimir Tolmachev
Imaging of expression of therapeutic targets may enable patients' stratification for targeted treatments. The use of small radiolabeled probes based on the heavy-chain variable region of heavy-chain-only immunoglobulins or non-immunoglobulin scaffolds permits rapid localization of radiotracers in tumors and rapid clearance from normal tissues. This makes high-contrast imaging possible on the day of injection. This mini-review focuses on small proteins for radionuclide-based imaging that would allow same-day imaging, with the emphasis on clinical applications and promising preclinical developments within the field of oncology...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Ana Dolinar, Metka Ravnik-Glavač, Damjan Glavač
Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease. Decades of research show that the etiology of this disease is affected by genetic, epigenetic and environmental factors rather than limited by a patient's genotype. The interaction between these factors is complex, and research has only begun to unravel this issue. The main epigenetic mechanisms, DNA methylation, miRNA, and histone modifications, can explain a portion of the disease complexity. However, the interplay among the epigenetic mechanisms themselves and with genetic factors remains largely uncharacterized...
March 12, 2018: Mechanisms of Ageing and Development
Weiyang Chen, Longfa Fang, Xiahe Huang, Haitao Ge, Jinlong Wang, Xiaorong Wang, Yuanya Zhang, Na Sui, Wu Xu, Yingchun Wang
Differential expression of cold-responsive proteins is necessary for cyanobacteria to acclimate to cold stress frequently occurring in their natural habitats. Accumulating evidence indicates that cold-induced expression of certain proteins is dependent on light illumination, but a systematic identification of light-dependent and/or light-independent cold-responsive proteins in cyanobacteria is still lacking. Herein, we comprehensively identified cold-responsive proteins in a model cyanobacterium Synechocystis sp...
March 12, 2018: Journal of Proteomics
Maioli E, Daveri E, Maellaro E, Ietta F, Cresti L, Valacchi G
In the past few years, we focused the interest on rottlerin, an old/new natural substance that, over the time, has revealed a number of cellular and molecular targets, all potentially implicated in the fight against cancer. Past and recent literature well demonstrated that rottlerin is an inhibitor of enzymes, transcription factors and signaling molecules that control cancer cell life and death. Although the rottlerin anticancer activity has been mainly ascribed to apoptosis and/or autophagy induction, recent findings unveiled the existence of additional mechanisms of toxicity...
March 12, 2018: Archives of Biochemistry and Biophysics
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