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https://www.readbyqxmd.com/read/29782832/nup159-weakens-gle1-binding-to-dbp5-but-does-not-accelerate-adp-release
#1
Emily V Wong, Shawn Gray, Wenxiang Cao, Rachel Montpetit, Ben Montpetit, Enrique M De La Cruz
Dbp5, DDX19 in humans, is an essential DEAD-box protein involved in mRNA export, which has also been linked to other cellular processes, including rRNA export and translation. Dbp5 ATPase activity is regulated by several factors, including RNA, the nucleoporin proteins Nup159 and Gle1, and the endogenous small molecule inositol hexakisphosphate (InsP6 ). To better understand how these factors modulate Dbp5 activity and how this modulation relates to in vivo RNA metabolism, a detailed characterization of the Dbp5 mechanochemical cycle in the presence of those regulators individually or together is necessary...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29779104/alternative-splicing-of-the-xmas-mrna-encoding-the-mrna-export-protein-in-drosophila-melanogaster
#2
D V Kopytova, Yu V Il'in, E N Nabirochkina
It is shown that Drosophila melanogaster has Xmas mRNA whose alternative splicing leads to the formation of three transcripts: Xmas, Xmas-2, and Xmas-1. As a result, three proteins are synthesized: Xmas, Xmas-2, and, presumably, Xmas-1. The size of the Xmas protein is close to the size of its homologue in humans. Adult flies contain large amounts of this protein, whereas in embryos it is absent.
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#3
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29772789/downregulation-of-the-s1p-transporter-spinster-homology-protein-2-spns2-exerts-an-anti-fibrotic-and-anti-inflammatory-effect-in-human-renal-proximal-tubular-epithelial-cells
#4
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29768216/the-rna-exosome-adaptor-zfc3h1-functionally-competes-with-nuclear-export-activity-to-retain-target-transcripts
#5
Toomas Silla, Evdoxia Karadoulama, Dawid Mąkosa, Michal Lubas, Torben Heick Jensen
Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+ ) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767852/membrane-tethered-syntaxin-4-locally-abrogates-e-cadherin-function-and-activates-smad-signals-contributing-to-asymmetric-mammary-epithelial-morphogenesis
#6
Yuina Hirose, Kota Shirai, Yohei Hirai
Spatial and temporal epithelial-mesenchymal transition (EMT) is a critical event for the generation of asymmetric epithelial architectures. We found that only restricted cell populations in the morphogenic mammary epithelia extrude syntaxin-4, a plasmalemmal t-SNARE protein, and that epithelial cell clusters with artificial heterogenic presentation of extracellular syntaxin-4 undergo asymmetric morphogenesis. A previous study revealed that inducible expression of cell surface syntaxin-4 causes EMT-like cell behaviors in the clonal mammary epithelial cells, where laminin-mediated signals were abolished so that cells readily succumb to initiate EMT...
May 16, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29758258/nuclear-mrna-surveillance-mechanisms-function-and-links-to-human-disease
#7
REVIEW
Pragyan Singh, Upasana Saha, Sunirmal Paira, Biswadip Das
Production of export-competent mRNAs involves transcription and a series of dynamic processing and modification events of pre-messenger RNAs in the nucleus. Mutations in the genes encoding the transcription and mRNP processing machinery and the complexities involved in the biogenesis events lead to the formation of aberrant messages. These faulty transcripts are promptly eliminated by the nuclear RNA exosome and its cofactors to safeguard the cells and organisms from genetic catastrophe. Mutations in the components of the core nuclear exosome and its cofactors lead to the tissue-specific dysfunction of exosomal activities, which are linked to diverse human diseases and disorders...
May 11, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29746542/depletion-of-mrna-export-regulator-dbp5-ddx19-gle1-or-ippk-that-is-a-key-enzyme-for-the-production-of-ip6-resulting-in-differentially-altered-cytoplasmic-mrna-expression-and-specific-cell-defect
#8
Masumi Okamura, Yasutaka Yamanaka, Maki Shigemoto, Yuya Kitadani, Yuhko Kobayashi, Taiho Kambe, Masaya Nagao, Issei Kobayashi, Katsuzumi Okumura, Seiji Masuda
DBP5, also known as DDX19, GLE1 and inositol hexakisphosphate (IP6) function in messenger RNA (mRNA) export at the cytoplasmic surface of the nuclear pore complex in eukaryotic cells. DBP5 is a DEAD-box RNA helicase, and its activity is stimulated by interactions with GLE1 and IP6. In addition, these three factors also have unique role(s). To investigate how these factors influenced the cytoplasmic mRNA expression and cell phenotype change, we performed RNA microarray analysis to detect the effect and function of DBP5, GLE1 and IP6 on the cytoplasmic mRNA expression...
2018: PloS One
https://www.readbyqxmd.com/read/29741478/srsf3-promotes-pluripotency-through-nanog-mrna-export-and-coordination-of-the-pluripotency-gene-expression-program
#9
Madara Ratnadiwakara, Stuart K Archer, Craig I Dent, Igor Ruiz de Los Mozos, Traude H Beilharz, Anja S Knaupp, Christian M Nefzger, Jose M Polo, Minna-Liisa Anko
The establishment and maintenance of pluripotency depend on precise coordination of gene expression. We establish serine-arginine rich splicing factor 3 (SRSF3) as an essential regulator of RNAs encoding key components of the mouse pluripotency circuitry, SRSF3 ablation resulting in the loss of pluripotency and its overexpression enhancing reprogramming. Strikingly, SRSF3 binds to the core pluripotency transcription factor Nanog mRNA to facilitate its nucleo-cytoplasmic export independent of splicing. In the absence of SRSF3 binding, Nanog mRNA is sequestered in the nucleus and protein levels are severely downregulated...
May 9, 2018: ELife
https://www.readbyqxmd.com/read/29736189/investigation-of-the-influence-of-high-glucose-on-molecular-and-genetic-responses-an-in-vitro-study-using-a-human-intestine-model
#10
Tugce Boztepe, Sukru Gulec
Background: Dietary glucose consumption has increased worldwide. Long-term high glucose intake contributes to the development of obesity and type 2 diabetes mellitus (T2DM). Obese people tend to eat glucose-containing foods, which can lead to an addiction to glucose, increased glucose levels in the blood and intestine lumen, and exposure of intestinal enterocytes to high dietary glucose. Recent studies have documented a role for enterocytes in glucose sensing. However, the molecular and genetic relationship between high glucose levels and intestinal enterocytes has not been determined...
2018: Genes & Nutrition
https://www.readbyqxmd.com/read/29730276/mechanism-of-n-6-methyladenosine-modification-and-its-emerging-role-in-cancer
#11
REVIEW
Sicong Zhang
N6 -methyladenosine (m6 A), the most prevalent internal methylation in messenger RNA (mRNA) that is deposited by m6 A methyltransferases, removed by m6 A demethylases and recognized by different RNA-binding proteins, distinguishes the transcripts through multilayer interactions with mRNA processing, export, degradation and translation machineries. m6 A plays an important role in regulation of gene expression for fundamental cellular processes and diverse physiological functions. Aberrant m6 A decorations lead to cancer but also have the potential to yield new therapies...
May 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29729018/the-role-of-dynamic-m-6-a-rna-methylation-in-photobiology
#12
Myles Robinson, Palak Shah, Yanhong Cui, Yu-Ying He
N6 -methyladenosine (m6 A) is the most abundant internal RNA modification among numerous post-transcriptional modifications identified in eukaryotic mRNA. m6 A modification of RNA is catalyzed by the "writer" m6 A methyltransferase enzyme complex, consisting of METTL3, METTL14, WTAP, and KIAA1429. The m6 A modification is reversible, and can be removed by "eraser" m6 A demethylase enzymes, namely, FTO and ALKBH5. The biological function of m6 A modification on RNA is carried out by RNA-binding effector proteins called "readers"...
May 4, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29728564/nuclear-egress-of-tdp-43-and-fus-occurs-independently-of-exportin-1-crm1
#13
Helena Ederle, Christina Funk, Claudia Abou-Ajram, Saskia Hutten, Eva B E Funk, Ralph H Kehlenbach, Susanne M Bailer, Dorothee Dormann
TDP-43 and FUS are nuclear proteins with multiple functions in mRNA processing. They play key roles in ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia), where they are partially lost from the nucleus and aggregate in the cytoplasm of neurons and glial cells. Defects in nucleocytoplasmic transport contribute to this pathology, hence nuclear import of both proteins has been studied in detail. However, their nuclear export routes remain poorly characterized and it is unclear whether aberrant nuclear export contributes to TDP-43 or FUS pathology...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29721575/iron-excess-upregulates-spns2-mrna-levels-but-reduces-sphingosine-1-phosphate-export-in-human-osteoblastic-mg-63-cells
#14
L Peltier, C Bendavid, T Cavey, M-L Island, M Doyard, P Leroyer, C Allain, M De Tayrac, M Ropert, O Loréal, P Guggenbuhl
We aimed to study the mechanisms involved in bone-related iron impairment by using the osteoblast-like MG-63 cell line. Our results indicate that iron impact the S1P/S1PR signalizing axis and suggest that iron can affect the S1P process and favor the occurrence of osteoporosis during chronic iron overload. INTRODUCTION: Systemic iron excess favors the development of osteoporosis, especially during genetic hemochromatosis. The cellular mechanisms involved are still unclear despite numerous data supporting a direct effect of iron on bone biology...
May 3, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29703953/structural-analysis-of-human-ars2-as-a-platform-for-co-transcriptional-rna-sorting
#15
Wiebke Manuela Schulze, Frank Stein, Mandy Rettel, Max Nanao, Stephen Cusack
ARS2 is a highly conserved metazoan protein involved in numerous aspects of nuclear RNA metabolism. As a direct partner of the nuclear cap-binding complex (CBC), it mediates interactions with diverse RNA processing and transport machineries in a transcript-dependent manner. Here, we present the human ARS2 crystal structure, which exhibits similarities and metazoan-specific differences to the plant homologue SERRATE, most notably an additional RRM domain. We present biochemical, biophysical and cellular interactome data comparing wild type and mutant ARS2 that identify regions critical for interactions with FLASH (involved in histone mRNA biogenesis), NCBP3 (a putative cap-binding protein involved in mRNA export) and single-stranded RNA...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29695716/regulation-of-yki-yap-subcellular-localization-and-hpo-signaling-by-a-nuclear-kinase-prp4k
#16
Yong Suk Cho, Jian Zhu, Shuangxi Li, Bing Wang, Yuhong Han, Jin Jiang
Hippo (Hpo) signaling pathway controls tissue growth by regulating the subcellular localization of Yorkie (Yki)/Yap via a cytoplasmic kinase cassette containing an upstream kinase Hpo/MST1/2 and a downstream kinase Warts (Wts)/Lats1/2. Here we show that PRP4K, a kinase involved in mRNA splicing, phosphorylates Yki/Yap in the nucleus to prevent its nuclear accumulation and restrict Hpo pathway target gene expression. PRP4K inactivation accelerates whereas excessive PRP4K inhibits Yki-driven tissue overgrowth...
April 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29686088/iron-promotes-oxidative-cell-death-caused-by-bisretinoids-of-retina
#17
Keiko Ueda, Hye Jin Kim, Jin Zhao, Ying Song, Joshua L Dunaief, Janet R Sparrow
Intracellular Fe plays a key role in redox active energy and electron transfer. We sought to understand how Fe levels impact the retina, given that retinal pigment epithelial (RPE) cells are also challenged by accumulations of vitamin A aldehyde adducts (bisretinoid lipofuscin) that photogenerate reactive oxygen species and photodecompose into damaging aldehyde- and dicarbonyl-bearing species. In mice treated with the Fe chelator deferiprone (DFP), intracellular Fe levels, as reflected in transferrin receptor mRNA expression, were reduced...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29683372/modulating-the-expression-of-chtop-a-versatile-regulator-of-gene-specific-transcription-and-mrna-export
#18
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29644261/detection-and-analysis-of-circular-rnas-by-rt-pcr
#19
Amaresh C Panda, Myriam Gorospe
Gene expression in eukaryotic cells is tightly regulated at the transcriptional and posttranscriptional levels. Posttranscriptional processes, including pre-mRNA splicing, mRNA export, mRNA turnover, and mRNA translation, are controlled by RNA-binding proteins (RBPs) and noncoding (nc)RNAs. The vast family of ncRNAs comprises diverse regulatory RNAs, such as microRNAs and long noncoding (lnc)RNAs, but also the poorly explored class of circular (circ)RNAs. Although first discovered more than three decades ago by electron microscopy, only the advent of high-throughput RNA-sequencing (RNA-seq) and the development of innovative bioinformatic pipelines have begun to allow the systematic identification of circRNAs (Szabo and Salzman, 2016; Panda et al ...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29618122/ddx49-is-an-rna-helicase-that-affects-translation-by-regulating-mrna-export-and-the-levels-of-pre-ribosomal-rna
#20
Sharad Awasthi, Mamta Verma, Arun Mahesh, Mohd Imran K Khan, Gayathri Govindaraju, Arumugam Rajavelu, Pavithra L Chavali, Sreenivas Chavali, Arunkumar Dhayalan
Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A)+ RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability...
March 30, 2018: Nucleic Acids Research
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