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https://www.readbyqxmd.com/read/27921095/journey-from-the-center-of-the-cell-the-intra-and-intercellular-transport-of-mrna
#1
Anna Kasprowicz-Maluśki, Wojciech Kwiatkowski, Alicja Starosta, Przemysław Wojtaszek
Transport and localized translation of mRNA is crucial for the proper spatiotemporal organization of proteins within cells. Distribution of RNAs to subcellular domains has recently emerged as a major mechanism for establishing functionally distinct compartments and structures in the cells. There is an emerging evidence that active transport of mRNA involves cytoskeleton and membrane trafficking pathways in fungi, plants and animals, suggesting that it is a common phenomenon among eukaryotes. The important highlights are that the RNA-binding proteins recognize the cargo mRNA and that RNPs are actively transported on the cytoskeletal tracks or co-transported with membranous compartments, such as the endoplasmic reticulum and endosomes...
December 6, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27903772/diverse-activities-of-viral-cis-acting-rna-regulatory-elements-revealed-using-multi-color-long-term-single-cell-imaging
#2
Ginger M Pocock, Laraine L Zimdars, Ming Yuan, Kevin W Eliceiri, Paul Ahlquist, Nathan M Sherer
Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other post-transcriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multi-color, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus) and an intron-retaining transcript encoded by the cellular NXF1 gene...
November 30, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27868086/links-between-mrna-splicing-mrna-quality-control-and-intellectual-disability
#3
Milo B Fasken, Anita H Corbett
In recent years, the impairment of RNA binding proteins that play key roles in the post-transcriptional regulation of gene expression has been linked to numerous neurological diseases. These RNA binding proteins perform critical mRNA processing steps in the nucleus, including splicing, polyadenylation, and export. In many cases, these RNA binding proteins are ubiquitously expressed raising key questions about why only brain function is impaired. Recently, mutations in the ZC3H14 gene, encoding an evolutionarily conserved, polyadenosine RNA binding protein, have been linked to a nonsyndromic form of autosomal recessive intellectual disability...
2016: RNA & Disease
https://www.readbyqxmd.com/read/27863346/a-diet-induced-sprague-dawley-rat-model-of-nonalcoholic-steatohepatitis-related-cirrhosis
#4
Mayuko Ichimura, Miki Masuzumi, Miku Kawase, Mika Sakaki, Shizuka Tamaru, Yasuo Nagata, Kazunari Tanaka, Kazuhito Suruga, Koichi Tsuneyama, Satoru Matsuda, Katsuhisa Omagari
Certain modified diets containing saturated fatty acids, cholesterol or fructose lead to the development of nonalcoholic steatohepatitis (NASH)-related fibrosis in rodents; however, progression to cirrhosis is rare. Experimental liver cirrhosis models have relied on genetic manipulation or administration of hepatotoxins. This study aimed to establish a reliable dietary model of NASH-related cirrhosis in a relatively short period. Male Sprague-Dawley rats (9 weeks of age) were randomly assigned to normal, high-fat (HF), or two types (1...
October 24, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27863241/the-chromatin-remodeler-isw1-is-a-quality-control-factor-that-surveys-nuclear-mrnp-biogenesis
#5
Anna Babour, Qingtang Shen, Julien Dos-Santos, Struan Murray, Alexandre Gay, Drice Challal, Milo Fasken, Benoît Palancade, Anita Corbett, Domenico Libri, Jane Mellor, Catherine Dargemont
Chromatin dynamics play an essential role in regulating DNA transaction processes, but it is unclear whether transcription-associated chromatin modifications control the mRNA ribonucleoparticles (mRNPs) pipeline from synthesis to nuclear exit. Here, we identify the yeast ISW1 chromatin remodeling complex as an unanticipated mRNP nuclear export surveillance factor that retains export-incompetent transcripts near their transcription site. This tethering activity of ISW1 requires chromatin binding and is independent of nucleosome sliding activity or changes in RNA polymerase II processivity...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27863235/a-new-path-through-the-nuclear-pore
#6
Alejandro Gozalo, Maya Capelson
Knowing the configuration of the nuclear pore is essential for appreciating the underlying mechanisms of nucleo-cytoplasmic communication. Now, Fernandez-Martinez et al. present a high-resolution structure of the cytoplasmic nuclear pore-mRNA export holo-complex, challenging our textbook depiction of this massive membrane-embedded complex.
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27856995/choline-protects-against-intestinal-failure-associated-liver-disease-in-parenteral-nutrition-fed-immature-rats
#7
Jie Zhu, Ting Lu, Fei Chen, Junkai Yan, Fan Chen, Qiaosen Zhang, Jifan Wang, Weihui Yan, Tingxi Yu, Qingya Tang, Wei Cai
BACKGROUND: Deficiency of choline, a required nutrient, is related to intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms. METHODS: Male Sprague-Dawley rats (4 weeks old) were fed AIN-93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites...
November 17, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27845231/streptozotocin-diabetes-increases-mrna-expression-of-ketogenic-enzymes-in-the-rat-heart
#8
George A Cook, Eduard N Lavrentyev, Kevin Pham, Edwards A Park
BACKGROUND: Diabetic cardiomyopathy develops in insulin-dependent diabetic patients who have no hypertension, cardiac hypertrophy or vascular disease. Diabetes increases cardiac fatty acid oxidation, but cardiac hypertrophy limits fatty acid oxidation. Here we examined effects of diabetes on gene expression in rat hearts. METHODS: We used oligonucleotide microarrays to examine effects of insulindependent diabetes in the rat heart. RTQ PCR confirmed results of microarrays...
November 11, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27833104/analysis-of-zinc-exporters-expression-in-prostate-cancer
#9
Chandra K Singh, Kareem M Malas, Caitlin Tydrick, Imtiaz A Siddiqui, Kenneth A Iczkowski, Nihal Ahmad
Maintaining optimal intracellular zinc (Zn) concentration is crucial for critical cellular functions. Depleted Zn has been associated with prostate cancer (PCa) progression. Solute carrier family 30 (SLC30A) proteins maintain cytoplasmic Zn balance by exporting Zn out to the extracellular space or by sequestering cytoplasmic Zn into intracellular compartments. In this study, we determined the involvement of Zn-exporters, SLC30A 1-10 in PCa, in the context of racial health disparity in human PCa samples obtained from European-American (EA) and African-American (AA) populations...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832591/a-herpesvirus-protein-selectively-inhibits-cellular-mrna-nuclear-export
#10
Danyang Gong, Yong Hoon Kim, Yuchen Xiao, Yushen Du, Yafang Xie, Kevin K Lee, Jun Feng, Nisar Farhat, Dawei Zhao, Sara Shu, Xinghong Dai, Sumit K Chanda, Tariq M Rana, Nevan J Krogan, Ren Sun, Ting-Ting Wu
Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27830674/-protein-complexes-coordinating-mrna-export-from-the-nucleus-into-the-cytoplasm
#11
M M Kurshakova, S G Georgieva, D V Kopytova
The molecular mechanisms that coordinate transcription, processing, mRNP assembly, and mRNA export from the nucleus through nuclear pores into the cytoplasm have been the focus of intense research in recent years. Data demonstrating a tight association between the processes involved in gene expression are considered. The main protein complexes that play a role in mRNA export are described. The complexes are recruited to mRNA at steps preceding the mRNA export. The functions that the complexes perform at particular steps of gene expression are analyzed, and protein complexes responsible for quality control of mRNP discussed...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27805000/regulation-of-rna-binding-proteins-affinity-to-export-receptors-enables-the-nuclear-basket-proteins-to-distinguish-and-retain-aberrant-mrnas
#12
M Soheilypour, M R K Mofrad
Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798559/targeting-the-atp-dependent-formation-of-herpesvirus-ribonucleoprotein-particle-assembly-as-an-antiviral-approach
#13
Sophie Schumann, Brian R Jackson, Ian Yule, Steven K Whitehead, Charlotte Revill, Richard Foster, Adrian Whitehouse
Human herpesviruses are responsible for a range of debilitating acute and recurrent diseases, including a number of malignancies. Current treatments are limited to targeting the herpesvirus DNA polymerases, but with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. Here, we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs)...
October 31, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27795436/naf1-regulates-hiv-1-latency-by-suppressing-viral-promoter-driven-gene-expression-in-primary-cd4-t-cells
#14
Chuan Li, Hai-Bo Wang, Wen-Dong Kuang, Xiao-Xin Ren, Shu-Ting Song, Huan-Zhang Zhu, Qiang Li, Li-Ran Xu, Hui-Jun Guo, Li Wu, Jian-Hua Wang
: HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating the LTR activity contribute to HIV-1 latency and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleo-cytoplasmic shuttling protein and regulates multiple cellular signal pathways and HIV-1 production. We have recently reported that the nucleus-located Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to the accumulated Gag production...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27791484/regulation-of-mrna-capping-in-the-cell-cycle
#15
Michael Aregger, Victoria H Cowling
The mRNA cap structure, which is added to nascent RNA pol II transcripts, recruits the protein complexes required for pre-mRNA transcript processing, mRNA export and translation initiation. The enzymes which catalyse mRNA cap synthesis are regulated by cellular signaling pathways which impact on their expression, localisation and activity. Here we discuss the recent observation that the mRNA cap methyltransferase, RNMT, is phosphorylated on Thr-77 by CDK1-cyclin B1, which regulates its activity and the proteins with which it interacts...
October 28, 2016: RNA Biology
https://www.readbyqxmd.com/read/27791013/herpes-simplex-virus-icp27-regulates-alternative-pre-mrna-polyadenylation-and-splicing-in-a-sequence-dependent-manner
#16
Shuang Tang, Amita Patel, Philip R Krause
The herpes simplex virus (HSV) infected cell culture polypeptide 27 (ICP27) protein is essential for virus infection of cells. Recent studies suggested that ICP27 inhibits splicing in a gene-specific manner via an unknown mechanism. Here, RNA-sequencing revealed that ICP27 not only inhibits splicing of certain introns in <1% of cellular genes, but also can promote use of alternative 5' splice sites. In addition, ICP27 induced expression of pre-mRNAs prematurely cleaved and polyadenylated from cryptic polyadenylation signals (PAS) located in intron 1 or 2 of ∼1% of cellular genes...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27780845/the-c-terminus-of-pcf11-forms-a-novel-zinc-finger-structure-that-plays-an-essential-role-in-mrna-3-end-processing
#17
Fan Yang, Peter Hsu, Susan D Lee, Wen Yang, Derick Hoskinson, Weihao Xu, Claire Moore, Gabriele Varani
3'-end processing of pre-mRNAs prior to packaging and export to the cytoplasm of the mature transcript is a highly regulated process executed by several tens of protein factors that recognize poorly conserved RNA signals. Among them is Pcf11, a highly conserved, multi-domain protein that links transcriptional elongation, 3'-end processing and transcription termination. Here we report the structure and biochemical function of Pcf11's C-terminal domain, which is conserved from yeast to humans. We identify a novel zinc finger fold, resembling a trillium flower...
October 25, 2016: RNA
https://www.readbyqxmd.com/read/27771699/cardiac-hepcidin-expression-associates-with-injury-independent-of-iron
#18
G Fenna van Breda, Lennart G Bongartz, Wenqing Zhuang, Rachel P L van Swelm, Jeanne Pertijs, Branko Braam, Maarten-Jan Cramer, Dorine W Swinkels, Pieter A Doevendans, Marianne C Verhaar, Roos Masereeuw, Jaap A Joles, Carlo A J M Gaillard
BACKGROUND: Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content...
2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27765368/the-chloroform-extract-of-cyclocarya-paliurus-attenuates-high-fat-diet-induced-non-alcoholic-hepatic-steatosis-in-sprague-dawley-rats
#19
Zi Lin, Zheng-Feng Wu, Cui-Hua Jiang, Qing-Wen Zhang, Sheng Ouyang, Chun-Tao Che, Jian Zhang, Zhi-Qi Yin
BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27754875/global-analysis-of-pre-mrna-subcellular-localization-following-splicing-inhibition-by-spliceostatin-a
#20
Rei Yoshimoto, Daisuke Kaida, Masaaki Furuno, A Maxwell Burroughs, Shohei Noma, Harukazu Suzuki, Yumi Kawamura, Yoshihide Hayashizaki, Akila Mayeda, Minoru Yoshida
Spliceostatin A (SSA) is a methyl ketal derivative of FR901464, a potent antitumor compound isolated from a culture broth of Pseudomonas sp. no. 2663. These compounds selectively bind to the essential spliceosome component SF3b, a subcomplex of the U2 snRNP, to inhibit pre-mRNA splicing. However, the mechanism of SSA's antitumor activity is unknown. It is noteworthy that SSA causes accumulation of a truncated form of the CDK inhibitor protein p27 translated from CDKN1B pre-mRNA, which is involved in SSA-induced cell-cycle arrest...
October 17, 2016: RNA
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