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Mrna export

Lina Rustanti, Hongping Jin, Dongsheng Li, Mary Lor, Haran Sivakumaran, David Harrich
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral mRNA from the nucleus to the cytoplasm and transcription of viral mRNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2 (a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-ZsGreen1 to human T cells...
March 14, 2018: Virologica Sinica
Christina Pfaff, Hans F Ehrnsberger, Maria Flores-Tornero, Brian B Soerensen, Thomas Schubert, Gernot Längst, Joachim Griesenbeck, Stefanie Sprunck, Marion Grasser, Klaus D Grasser
The regulated transport of mRNAs from the cell nucleus to the cytosol is a critical step linking transcript synthesis and processing with translation. However, in plants, only few of the factors that act in the mRNA export pathway have been functionally characterised. Flowering plant genomes encode several members of the ALY protein family, which function as mRNA export factors in other organisms. Arabidopsis thaliana ALY1-4 are commonly detected in root and leaf cells, but are differentially expressed in reproductive tissue...
March 14, 2018: Plant Physiology
Sammy M Tabbah, Catalin S Buhimschi, Katherine Rodewald-Millen, Christopher R Pierson, Vineet Bhandari, Philip Samuels, Irina A Buhimschi
OBJECTIVE:  Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN:  Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS ( n  = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS ( n  = 51, GA 26 ± 1 weeks)...
February 2, 2018: American Journal of Perinatology
Navroop K Dhaliwal, Kamelia Miri, Scott Davidson, Hala Tamim El Jarkass, Jennifer A Mitchell
Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation...
March 1, 2018: Stem Cell Reports
Taewook Kang, Pia Jensen, Vita Solovyeva, Jonathan R Brewer, Martin R Larsen
Characterization of molecular mechanisms underlying pancreatic β-cell function in relation to glucose-stimulated insulin secretion is incomplete, especially with respect to global response in the nuclear environment. Here, we focus on the characterization of proteins in the nuclear environment of β-cells after brief, high glucose-stimulation. We compared purified nuclei derived from β-cells stimulated with 17mM glucose for 0, 2, and 5 minutes using quantitative proteomics, a time frame that most likely does not result in translation of new protein in the cell...
March 8, 2018: Journal of Proteome Research
Ji Heon Noh, Kyoung Mi Kim, Waverly G McClusky, Kotb Abdelmohsen, Myriam Gorospe
Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions...
March 8, 2018: Wiley Interdisciplinary Reviews. RNA
Elena V Kupriyanova, Maria A Sinetova, Vladimir S Bedbenov, Natalia A Pronina, Dmitry A Los
Carbonic anhydrase (CA) EcaA of Synechococcus elongatus PCC 7942 was previously characterized as a putative extracellular α-class CA, however, its activity was never verified. Here we show that EcaA possesses specific CA activity, which is inhibited by ethoxyzolamide. An active EcaA was expressed in heterologous bacterial system, which supports the formation of disulfide bonds, as a full-length protein (EcaA+L) and as a mature protein that lacks a leader peptide (EcaA-L). EcaA-L exhibited higher specific activity compared to EcaA+L...
February 27, 2018: Microbiology
Yoav Lubelsky, Igor Ulitsky
Long noncoding RNAs (lncRNAs) are emerging as key players in multiple cellular pathways1 , but their modes of action and how those are dictated by sequence remain unclear. lncRNAs tend to be enriched in the nuclear fraction, whereas most mRNAs are overtly cytoplasmic2 , although several studies have found that hundreds of mRNAs in various cell types are retained in the nucleus3,4 . It is thus conceivable that some mechanisms that promote nuclear enrichment are shared between lncRNAs and mRNAs. In order to identify elements that can force nuclear localization in lncRNAs and mRNAs we screened libraries of short fragments tiled across nuclear RNAs, which were cloned into the untranslated regions of an efficiently exported mRNA...
January 24, 2018: Nature
Aditya Ganju, Subhash C Chauhan, Bilal Bin Hafeez, Kyle Doxtater, Manish K Tripathi, Nadeem Zafar, Murali M Yallapu, Rakesh Kumar, Meena Jaggi
BACKGROUND: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1. METHODS: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were determined using western blotting and reverse-transcription quantitative real-time PCR...
February 20, 2018: British Journal of Cancer
Margaretha A Skowron, Margarita Melnikova, Joep G H van Roermund, Andrea Romano, Peter Albers, Juergen Thomale, Wolfgang A Schulz, Günter Niegisch, Michèle J Hoffmann
Therapeutic efficacy of cisplatin-based treatment of late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their cisplatin response, and determined the expression of molecules involved in cisplatin transport and detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and Survivin were applied to investigate their ability to sensitise towards cisplatin...
February 16, 2018: International Journal of Molecular Sciences
Syohei Takaki, Ko Eto
We have demonstrated that the loss of programmed cell death 4 (Pdcd4), a translation inhibitor, induces apoptosis; however, when, where, and how Pdcd4 decreases in response to apoptotic stimuli and, conversely, exerts the anti-apoptotic function within normal cells are incompletely understood. Endogenous Pdcd4 was present in both the cytoplasm and nucleus of cells that survived. In cells that had committed to die by apoptotic stimuli, cytoplasmic Pdcd4 was lost more slowly than was nuclear Pdcd4; eventually, Pdcd4 remaining in the cytoplasm was lost and then apoptotic events were induced...
February 13, 2018: Molecular and Cellular Biochemistry
Chenpeng Xiao, Qilin Yu, Bing Zhang, Jianrong Li, Dan Zhang, Mingchun Li
AIM: In eukaryotes, the nuclear export of mRNAs is essential for gene expression and regulations of numerous cellular processes. This study aimed to identify the mRNA export factor Sac3 in Candida albicans. MATERIALS & METHODS: A sac3Δ/Δ mutant was obtained using PCR-mediated homologous recombination. RESULTS: Disruption of SAC3 caused abnormal accumulation of mRNA in the nuclei. Further investigations revealed that sac3Δ/Δ mutant exhibited a severely growth defect, which was related to abnormal aggregation of microtubules...
February 13, 2018: Future Microbiology
M Soheilypour, M Mofrad
Despite extensive research on how mRNAs are quality controlled prior to export into the cytoplasm, the exact underlying mechanisms are still under debate. Specifically, it is unclear how quality control proteins at the entry of the nuclear pore complex (NPC) distinguish normal and aberrant mRNAs. While some of the involved components are suggested to act as switches and recruit different factors to normal versus aberrant mRNAs, some experimental and computational evidence suggests that the combined effect of the regulated stochastic interactions between the involved components could potentially achieve an efficient quality control of mRNAs...
February 12, 2018: Nucleus
Manon Torres, Denis Becquet, Jean-Louis Franc, Anne-Marie François-Bellan
The circadian clock drives daily rhythms of multiple physiological processes, allowing organisms to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of at least 30% of expressed genes. While the ability for the endogenous timekeeping system to generate a 24-hr cycle is a cell-autonomous mechanism based on negative autoregulatory feedback loops of transcription and translation involving core-clock genes and their protein products, it is now increasingly evident that additional mechanisms also govern the circadian oscillations of clock-controlled genes...
February 9, 2018: Wiley Interdisciplinary Reviews. RNA
Adrian P Mansini, Maria J Lorenzo Pisarello, Kristen M Thelen, Maetzin Cruz-Reyes, Estanislao Peixoto, Sujeong Jin, Brynn N Howard, Christy E Trussoni, Gabriella B Gajdos, Nicholas F LaRusso, Maria J Perugorria, Jesus M Banales, Sergio A Gradilone
Cholangiocytes normally express primary cilia, a multisensory organelle that detects signals from the cellular environment. Cilia are significantly reduced in cholangiocarcinoma (CCA) by a mechanism involving overexpression of histone deacetylase 6 (HDAC6). Despite HDAC6 overexpression in CCA, we found no differences in its mRNA level, suggesting a post-transcriptional regulation, possibly involving miRNAs. Here we describe that at least two HDAC6-targeting miRNAs, miR-433 and miR-22, are downregulated in CCA both in vitro and in vivo...
February 6, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hanzhong Ke, Mingyuan Han, Qingzhan Zhang, Raymond Rowland, Maureen Kerrigan, Dongwan Yoo
Porcine reproductive and respiratory syndrome virus (PRRSV) has the ability to suppress the type I interferons (IFNs-α/β) induction to facilitate its survival during infection, and the nsp1 protein of PRRSV has been identified as the potent IFN antagonist. The nsp1β subunit of nsp1 has also been shown to block the host mRNA nuclear export as one of the mechanisms to suppress host antiviral protein production. The SAP motif in nsp1β is the functional motif for both IFN suppression and host mRNA nuclear retention, and using infectious clones, two mutant viruses vL126A and vL135A have been generated...
February 2, 2018: Virology
Arianna Piserà, Adele Campo, Salvatore Campo
In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'-UTRs of most eukaryotic mRNAs. Combined with other initiation factors, eIF4E mediates the mRNA recruitment on ribosomes to start the translation...
January 29, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
Dongjun Dai, Hanying Wang, Liyuan Zhu, Hongchuan Jin, Xian Wang
N6-methyladenosine (m6A) is the most abundant mRNA modification. With the development of antibody-based sequencing technologies and the findings of m6A-related "writers", "erasers", and "readers", the relationships between m6A and mRNA metabolism are emerging. The m6A modification influences almost every step of RNA metabolism that comprises mRNA processing, mRNA exporting from nucleus to cytoplasm, mRNA translation, mRNA decay, and the biogenesis of long-non-coding RNA (lncRNA) and microRNA (miRNA). Recently, more and more studies have found m6A is associated with cancer, contributing to the self-renewal of cancer stem cell, promotion of cancer cell proliferation, and resistance to radiotherapy or chemotherapy...
January 26, 2018: Cell Death & Disease
Adrienn Pethő, Yinghua Chen, Anne George
PURPOSE OF REVIEW: Exosomes are membrane vesicles that are released by most cell types into the extracellular environment. The purpose of this article is to discuss the main morphological features and contents of bone-derived exosomes, as well as their major isolation and physical characterization techniques. Furthermore, we present various scenarios and discuss potential clinical applications of bone-derived exosomes in bone repair and regeneration. RECENT FINDINGS: Exosomes were believed to be nanosized vesicles derived from the multivesicular body...
February 2018: Current Osteoporosis Reports
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