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https://www.readbyqxmd.com/read/28199839/the-survival-of-motor-neuron-protein-acts-as-a-molecular-chaperone-for-mrnp-assembly
#1
Paul G Donlin-Asp, Claudia Fallini, Jazmin Campos, Ching-Chieh Chou, Megan E Merritt, Han C Phan, Gary J Bassell, Wilfried Rossoll
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3' UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28198434/jerantinine-a-induces-tumor-specific-cell-death-through-modulation-of-splicing-factor-3b-subunit-1-sf3b1
#2
Felicia Fei-Lei Chung, Perry Faith Tze Ming Tan, Vijay Joseph Raja, Boon-Shing Tan, Kuan-Hon Lim, Toh-Seok Kam, Ling-Wei Hii, Si Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Li-Zhe Wong, Wai Keat Yam, Chun Wai Mai, Tracey D Bradshaw, Chee-Onn Leong
Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195221/transcriptome-analysis-around-the-onset-of-strawberry-fruit-ripening-uncovers-an-important-role-of-oxidative-phosphorylation-in-ripening
#3
Qing-Hua Wang, Cheng Zhao, Miao Zhang, Yu-Zhong Li, Yuan-Yue Shen, Jia-Xuan Guo
Although much progress has been made towards understanding the ripening of non-climacteric fruit using the strawberry as a model plant, the defined molecular mechanisms remain unclear. Here, RNA-sequencing was performed using four cDNA libraries around the onset of ripening, and a total of 31,793 unigenes and 335 pathways were annotated including the top five pathways, which were involved in ribosome, spliceosome, protein processing, plant-pathogen interaction and plant hormone signaling, and the important DEGs related to ripening were annotated to be mainly involved in protein translation and processing, sugar metabolism, energy metabolism, phytohormones, antioxidation, pigment and softening, especially finding a decreased trend of oxidative phosphorylation during red-coloring...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193846/protein-4-1r-exon-16-3-splice-site-activation-requires-coordination-among-tia1-pcbp1-and-rbm39-during-terminal-erythropoiesis
#4
Shu-Ching Huang, Henry S Zhang, Brian Yu, Ellen McMahon, Dan T Nguyen, Faye H Yu, Alexander C Ou, Jennie Park Ou, Edward J Benz
Exon 16 of protein 4.1R encodes a spectrin/actin-binding peptide critical for erythrocyte membrane stability. Its expression during erythroid differentiation is regulated by alternative pre-mRNA splicing. A UUUUCCCCCC-motif situated between the branch point and the 3' splice site is crucial for inclusion. We show that the "UUUU" region and the last 3 C's in this motif are necessary for the binding of splicing factors TIA1 and Pcbp1, and that these proteins appear to act in a collaborative manner to enhance exon 16 inclusion...
February 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28192940/analysis-of-tertiary-interactions-between-sart3-and-u6-small-nuclear-rna-using-modified-nanocapillaries
#5
Choongman Lee, Joon Kyu Park, Yeoan Youn, Joo Hyoung Kim, Kyo-Seok Lee, Nak-Kyoon Kim, Eunji Kim, Eunice Eunkyeong Kim, Kyung-Hwa Yoo
We employed modified glass nanocapillaries to investigate interactions between the RNA-binding protein, known as cell carcinoma antigen recognized by T cells-3 (SART3), and the noncoding spliceosome component, U6 small nuclear RNA (snRNA), at the single-molecule level. We functionalized the nanocapillaries with U6 snRNA fragments, which were hybridized to DNA molecules and then covalently attached to the nanocapillary surface. When transported through the modified nanocapillaries, two different SART3-derived constructs, HAT-RRM1-RRM2 and RRM1-RRM2, exhibited resistive ionic current pulses with different dwell times, which represented their different binding affinities to tethered U6 snRNAs...
February 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28192473/potential-effect-of-spliceosome-inhibition-in-small-cell-lung-cancer-irrespective-of-the-myc-status
#6
Kenichi Suda, Leslie Rozeboom, Hui Yu, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
Small cell lung cancer (SCLC) is a highly aggressive malignancy with few therapeutic advances in the treatment in recent decades. Based on a recent study that identified the spliceosome as a therapeutic vulnerability in MYC-driven breast cancers, we evaluated the efficacy of a spliceosome inhibitor in SCLC cell lines and analyzed the correlation with MYC status. Among 23 SCLC cell lines examined, eight showed high MYC protein expression (> 80% positive cells) by immunohistochemistry (IHC), while 10 cell lines demonstrated no staining for MYC...
2017: PloS One
https://www.readbyqxmd.com/read/28190732/the-macronuclear-genome-of-stentor-coeruleus-reveals-tiny-introns-in-a-giant-cell
#7
Mark M Slabodnick, J Graham Ruby, Sarah B Reiff, Estienne C Swart, Sager Gosai, Sudhakaran Prabakaran, Ewa Witkowska, Graham E Larue, Susan Fisher, Robert M Freeman, Jeremy Gunawardena, William Chu, Naomi A Stover, Brian D Gregory, Mariusz Nowacki, Joseph Derisi, Scott W Roy, Wallace F Marshall, Pranidhi Sood
The giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor [1, 2] is a heterotrichous ciliate distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan [3], were attracted to the system because of its regenerative abilities-if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality [2, 3]...
February 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28188674/microexons-discovery-regulation-and-function
#8
REVIEW
Dmytro Ustianenko, Sebastien M Weyn-Vanhentenryck, Chaolin Zhang
The importance of RNA splicing in numerous cellular processes is well established. However, an underappreciated aspect is the ability of the spliceosome to recognize a set of very small (3-30 nucleotide, 1-10 amino acid) exons named microexons. Despite their small size, microexons and their regulation through alternative splicing have now been shown to play critical roles in protein and system function. Here we review the discovery of microexons over time and the mechanisms by which their splicing is regulated, including recent progress made through deep RNA sequencing...
February 11, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28177281/copy-number-and-gene-dependency-analysis-reveals-partial-copy-loss-of-wild-type-sf3b1-as-a-novel-cancer-vulnerability
#9
Brenton R Paolella, William J Gibson, Laura M Urbanski, John A Alberta, Travis I Zack, Pratiti Bandopadhayay, Caitlin A Nichols, Pankaj K Agarwalla, Meredith S Brown, Rebecca Lamothe, Yong Yu, Peter S Choi, Esther A Obeng, Dirk Heckl, Guo Wei, Belinda Wang, Aviad Tsherniak, Francisca Vazquez, Barbara A Weir, David E Root, Glenn S Cowley, Sara J Buhrlage, Charles D Stiles, Benjamin L Ebert, William C Hahn, Robin Reed, Rameen Beroukhim
Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28165654/identification-of-proteasomal-catalytic-subunit-psma6-as-a-therapeutic-target-for-lung-cancer
#10
Tomohiko Kakumu, Mitsuo Sato, Daiki Goto, Toshio Kato, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Takayuki Fukui, Kohei Yokoi, Yoshitaka Sekido, Luc Girard, John D Minna, Lauren A Byers, John V Heymach, Kevin R Coombes, Masashi Kondo, Yoshinori Hasegawa
To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilisation of genome-wide expression and copy number data. shRNA screening targeting 5,043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28157316/a-shotgun-proteomics-approach-reveals-a-new-toxic-role-for-alzheimer-s-disease-a%C3%AE-peptide-spliceosome-impairment
#11
Domenico Nuzzo, Luigi Inguglia, Jessica Walters, Pasquale Picone, Marta Di Carlo
Proteomic changes have been described in many neurodegenerative diseases including Alzheimer's disease (AD). However, the early events in the onset of the pathology are yet to be fully elucidated. A cell model system in which LAN5 neuroblastoma cells were incubated for a short time with a recombinant form of Aβ42 (rAβ42) was utilized. Proteins extracted from these cells were subjected to shotgun proteomics analysis by LTQ-Orbitrap-MS followed by label-free quantitation. By bioinformatics tools we found that the most significant of those found to be up-regulated were related to cytoskeletal dynamics (Rho related) and membrane related processes...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28132896/genetics-and-biochemistry-remain-essential-in-the-structural-era-of-the-spliceosome
#12
REVIEW
Megan Mayerle, Christine Guthrie
The spliceosome is not a single macromolecular machine. Rather it is a collection of dynamic heterogeneous subcomplexes that rapidly interconvert throughout the course of a typical splicing cycle. Because of this, for many years the only high resolution structures of the spliceosome available were of smaller, isolated protein or RNA components. Consequently much of our current understanding of the spliceosome derives from biochemical and genetic techniques. Now with the publication of multiple, high resolution structures of the spliceosome, some question the relevance of traditional biochemical and genetic techniques to the splicing field...
January 26, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28132030/usp15-regulates-dynamic-protein-protein-interactions-of-the-spliceosome-through-deubiquitination-of-prp31
#13
Tanuza Das, Joon Kyu Park, Jinyoung Park, Eunji Kim, Michael Rape, Eunice EunKyeong Kim, Eun Joo Song
No abstract text is available yet for this article.
January 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28125669/stably-expressed-genes-involved-in-basic-cellular-functions
#14
Kejian Wang, Vikrant Vijay, James C Fuscoe
Stably Expressed Genes (SEGs) whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age) in both sexes of F344 rats (n = 4/group; 320 samples). Expression changes (calculated as the maximum expression / minimum expression for each gene) of >19000 genes across organs, ages, and sexes ranged from 2...
2017: PloS One
https://www.readbyqxmd.com/read/28118396/correction-spliceosome-snrnp200-promotes-viral-rna-sensing-and-irf3-activation-of-antiviral-response
#15
Nicolas Tremblay, Martin Baril, Laurent Chatel-Chaix, Salwa Es-Saad, Alex Young Park, Robert K Koenekoop, Daniel Lamarre
[This corrects the article DOI: 10.1371/journal.ppat.1005772.].
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103691/sudemycin-k-a-synthetic-antitumor-splicing-inhibitor-variant-with-improved-activity-and-versatile-chemistry
#16
Kamil Makowski, Luisa Vigevani, Fernando Albericio, Juan Valcárcel, Mercedes Álvarez
Important links exist between the process of pre-mRNA splicing and cancer, as illustrated by the frequent mutation of splicing factors in tumors and the emergence of various families of antitumor drugs that target components of the splicing machinery, notably SF3B1, a protein subunit of spliceosomal U2 small nuclear ribonucleoprotein particle (snRNP). Sudemycins are synthetic compounds that harbor a pharmacophore common to various classes of splicing inhibitors. Here, we describe the synthesis and functional characterization of novel sudemycin analogues that functionally probe key chemical groups within this pharmacophore...
20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28102760/phf13-a-new-player-involved-in-rna-polymerase-ii-transcriptional-regulation-and-co-transcriptional-splicing
#17
Alisa Fuchs, Marcos Torroba, Sarah Kinkley
We recently identified PHF13 as an H3K4me2/3 chromatin reader and transcriptional co-regulator. We found that PHF13 interacts with RNAPIIS5P and PRC2 stabilizing their association with active and bivalent promoters. Furthermore, mass spectrometry analysis identified ∼50 spliceosomal proteins in PHF13s interactome. Here, we will discuss the potential role of PHF13 in RNAPII pausing and co-transcriptional splicing.
January 19, 2017: Transcription
https://www.readbyqxmd.com/read/28095062/microrna-196a-as-a-potential-diagnostic-biomarker-for-esophageal-squamous-cell-carcinoma
#18
Mona Fendereski, Mohammad Farid Zia, Mohammad Shafiee, Forousan Safari, Mohammad Hosien Saneie, Manoochehr Tavassoli
We observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC...
January 17, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28092684/biallelic-mutations-in-the-3-exonuclease-toe1-cause-pontocerebellar-hypoplasia-and-uncover-a-role-in-snrna-processing
#19
Rea M Lardelli, Ashleigh E Schaffer, Veerle R C Eggens, Maha S Zaki, Stephanie Grainger, Shashank Sathe, Eric L Van Nostrand, Zinayida Schlachetzki, Basak Rosti, Naiara Akizu, Eric Scott, Jennifer L Silhavy, Laura Dean Heckman, Rasim Ozgur Rosti, Esra Dikoglu, Anne Gregor, Alicia Guemez-Gamboa, Damir Musaev, Rohit Mande, Ari Widjaja, Tim L Shaw, Sebastian Markmiller, Isaac Marin-Valencia, Justin H Davies, Linda de Meirleir, Hulya Kayserili, Umut Altunoglu, Mary Louise Freckmann, Linda Warwick, David Chitayat, Susan Blaser, Ahmet Okay Çağlayan, Kaya Bilguvar, Huseyin Per, Christina Fagerberg, Henrik T Christesen, Maria Kibaek, Kimberly A Aldinger, David Manchester, Naomichi Matsumoto, Kazuhiro Muramatsu, Hirotomo Saitsu, Masaaki Shiina, Kazuhiro Ogata, Nicola Foulds, William B Dobyns, Neil C Chi, David Traver, Luigina Spaccini, Stefania Maria Bova, Stacey B Gabriel, Murat Gunel, Enza Maria Valente, Marie-Cecile Nassogne, Eric J Bennett, Gene W Yeo, Frank Baas, Jens Lykke-Andersen, Joseph G Gleeson
Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg(2+)-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092261/structural-insights-into-the-mechanism-of-the-deah-box-rna-helicase-prp43
#20
Marcel J Tauchert, Jean-Baptiste Fourmann, Reinhard Lührmann, Ralf Ficner
The DEAH-box helicase Prp43 is a key player in pre-mRNA splicing as well as the maturation of rRNAs. The exact modus operandi of Prp43 and of all other spliceosomal DEAH-box RNA helicases is still elusive. Here, we report crystal structures of Prp43 complexes in different functional states and the analysis of structure-based mutants providing insights into the unwinding and loading mechanism of RNAs. The Prp43•ATP-analog•RNA complex shows the localization of the RNA inside a tunnel formed by the two RecA-like and C-terminal domains...
January 16, 2017: ELife
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