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https://www.readbyqxmd.com/read/28820318/7sk-small-nuclear-rna-a-multifunctional-transcriptional-regulatory-rna-with-gene-specific-features
#1
Sylvain Egloff, Cécilia Studniarek, Tamás Kiss
The 7SK small nuclear RNA is a multifunctional transcriptional regulatory RNA that controls the nuclear activity of the positive transcription elongation factor b (P-TEFb), specifically targets P-TEFb to the promoter regions of selected protein-coding genes and promotes transcription of RNA polymerase II-specific spliceosomal small nuclear RNA genes.
August 18, 2017: Transcription
https://www.readbyqxmd.com/read/28818345/mobile-group-ii-introns-as-ancestral-eukaryotic-elements
#2
REVIEW
Olga Novikova, Marlene Belfort
The duality of group II introns, capable of carrying out both self-splicing and retromobility reactions, is hypothesized to have played a profound role in the evolution of eukaryotes. These introns likely provided the framework for the emergence of eukaryotic retroelements, spliceosomal introns and other key components of the spliceosome. Group II introns are found in all three domains of life and are therefore considered to be exceptionally successful mobile genetic elements. Initially identified in organellar genomes, group II introns are found in bacteria, chloroplasts, and mitochondria of plants and fungi, but not in nuclear genomes...
August 14, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28808137/regulatory-rnps-a-novel-class-of-ribonucleoproteins-that-potentially-contribute-to-ribosome-heterogeneity
#3
Aaron R Poole, Ian Vicino, Hironori Adachi, Yi-Tao Yu, Michael D Hebert
Many ribonucleoproteins (RNPs), which are comprised of non-coding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here we provide data that these RNAs become part of RNPs we term regulatory RNPs (regRNPs)...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28806086/role-of-electrostatics-in-protein-rna-binding-the-global-vs-the-local-energy-landscape
#4
Zhaleh Ghaemi, Irisbel Guzman, David Gnutt, Zaida Luthey-Schulten, Martin Gruebele
U1A protein - stem loop 2 RNA association is a basic step in the assembly of the spliceosomal U1 small nuclear ribonucleoprotein. Long-range electrostatic interactions due to the positive charge of U1A are thought to provide high binding affinity for the negatively charged RNA. Short range interactions, such as hydrogen bonds and contacts between RNA bases and protein side chains, favor a specific binding site. Here, we propose that electrostatic interactions are as important as local contacts in biasing the protein-RNA energy landscape towards a specific binding site...
August 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28792546/host-plant-driven-transcriptome-plasticity-in-the-salivary-glands-of-the-cabbage-looper-trichoplusia-ni
#5
Loren J Rivera-Vega, David A Galbraith, Christina M Grozinger, Gary W Felton
Generalist herbivores feed on a wide array of plants and need to adapt to varying host qualities and defenses. One of the first insect derived secretions to come in contact with the plant is the saliva. Insect saliva is potentially involved in both the pre-digestion of the host plant as well as induction/suppression of plant defenses, yet how the salivary glands respond to changes in host plant at the transcriptional level is largely unknown. The objective of this study was to determine how the labial salivary gland transcriptome varies according to the host plant on which the insect is feeding...
2017: PloS One
https://www.readbyqxmd.com/read/28792005/splicing-and-transcription-touch-base-co-transcriptional-spliceosome-assembly-and-function
#6
REVIEW
Lydia Herzel, Diana S M Ottoz, Tara Alpert, Karla M Neugebauer
Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length and generates a flexible RNA copy of the DNA template. This nascent RNA harbours introns that are removed by the spliceosome, which is a megadalton ribonucleoprotein complex that positions the distant ends of the intron into its catalytic centre. Emerging evidence that the catalytic spliceosome is physically close to Pol II in vivo implies that transcription and splicing occur on similar timescales and that the transcription and splicing machineries may be spatially constrained...
August 9, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#7
Elizabeta Rojas, Luis Corchete, Laura San Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemi Puig, Ramón García-Sanz, Maria Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
<br />The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.<br /><br />Experimental Design:  <p>Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28781166/cryo-em-structure-of-a-pre-catalytic-human-spliceosome-primed-for-activation
#8
Karl Bertram, Dmitry E Agafonov, Olexandr Dybkov, David Haselbach, Majety N Leelaram, Cindy L Will, Henning Urlaub, Berthold Kastner, Reinhard Lührmann, Holger Stark
Little is known about the spliceosome's structure before its extensive remodeling into a catalytically active complex. Here, we report a 3D cryo-EM structure of a pre-catalytic human spliceosomal B complex. The U2 snRNP-containing head domain is connected to the B complex main body via three main bridges. U4/U6.U5 tri-snRNP proteins, which are located in the main body, undergo significant rearrangements during tri-snRNP integration into the B complex. These include formation of a partially closed Prp8 conformation that creates, together with Dim1, a 5' splice site (ss) binding pocket, displacement of Sad1, and rearrangement of Brr2 such that it contacts its U4/U6 substrate and is poised for the subsequent spliceosome activation step...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28780959/structural-and-functional-analyses-of-the-spliceosome-requires-a-multi-disciplinary-approach
#9
EDITORIAL
Melanie D Ohi
No abstract text is available yet for this article.
August 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28780672/defective-splicing-of-the-rb1-transcript-is-the-dominant-cause-of-retinoblastomas
#10
Kamil J Cygan, Rachel Soemedi, Christy L Rhine, Abraham Profeta, Eileen L Murphy, Michael F Murray, William G Fairbrother
Defective splicing is a common cause of genetic diseases. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations with most mapping to the critical GT or AG nucleotides within the 5' and 3' splice sites. However, splicing mutations are underreported and the fraction of splicing mutations that compose all disease alleles varies greatly across disease gene. For example, there is a great excess (46%; ~threefold) of hereditary disease alleles that map to splice sites in RB1 that cause retinoblastoma...
August 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#11
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28768202/dual-rna-processing-roles-of-pat1b-via-cytoplasmic-lsm1-7-and-nuclear-lsm2-8-complexes
#12
Caroline Vindry, Aline Marnef, Helen Broomhead, Laure Twyffels, Sevim Ozgur, Georg Stoecklin, Miriam Llorian, Christopher W Smith, Juan Mata, Dominique Weil, Nancy Standart
Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5' to 3' mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28766300/a-cell-based-high-throughput-method-for-identifying-modulators-of-alternative-splicing
#13
Sika Zheng
Alternative splicing, a key regulatory process of gene expression, is controlled by trans-acting factors that recognize cis-elements in premature RNA transcripts to affect spliceosome assembly and splice site choices. Extracellular stimuli and signaling cascades can converge on RNA binding splicing regulators to affect alternative splicing. Defects in splicing regulation have been associated with various human diseases, and modification of disease-causing splicing events presents great therapeutic promise. Determining splicing regulators and/or upstream modulators has been difficult with low throughput, low sensitivity, and low specificity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28766287/single-molecule-analysis-of-pre-mrna-splicing-with-colocalization-single-molecule-spectroscopy-cosmos
#14
Joerg E Braun, Victor Serebrov
Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28766286/preparation-of-splicing-competent-nuclear-extract-from-mammalian-cells-and-in-vitro-pre-mrna-splicing-assay
#15
Maliheh Movassat, Hossein Shenasa, Klemens J Hertel
The ability to perform in vitro splicing assays has paved the way for in-depth studies of the mechanisms and machinery involved in the process of splicing. The in vitro splicing assay is a valuable experimental approach that combines the complexity of the spliceosome and regulatory systems with the flexibility of performing endless splicing and alternative splicing reactions. Through the use of crude nuclear extract and radiolabeled pre-mRNA, spliced mRNAs can be visualized using autoradiography for downstream analysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28760385/platelet-factor-xi-intracellular-localization-and-mrna-splicing-following-platelet-activation
#16
M Zucker, H Hauschner, U Seligsohn, N Rosenberg
BACKGROUND: The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation. OBJECTIVE: To determine whether FXI is also spliced upon activation and to discern the localization of FXI in platelets. METHODS: Localization of FXI in platelets was assessed by confocal immunofluorescence staining...
April 21, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28757210/introns-protect-eukaryotic-genomes-from-transcription-associated-genetic-instability
#17
Amandine Bonnet, Ana R Grosso, Abdessamad Elkaoutari, Emeline Coleno, Adrien Presle, Sreerama C Sridhara, Guilhem Janbon, Vincent Géli, Sérgio F de Almeida, Benoit Palancade
Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns increases R-loop formation, while insertion of an intron into an intronless gene suppresses R-loop accumulation and its deleterious impact on transcription and recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not splicing per se, is shown to be critical to attenuate R-loop formation and transcription-associated genetic instability...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28757206/nitric-oxide-regulates-protein-methylation-during-stress-responses-in-plants
#18
Jiliang Hu, Huanjie Yang, Jinye Mu, Tiancong Lu, Juli Peng, Xian Deng, Zhaosheng Kong, Shilai Bao, Xiaofeng Cao, Jianru Zuo
Methylation and nitric oxide (NO)-based S-nitrosylation are highly conserved protein posttranslational modifications that regulate diverse biological processes. In higher eukaryotes, PRMT5 catalyzes Arg symmetric dimethylation, including key components of the spliceosome. The Arabidopsis prmt5 mutant shows severe developmental defects and impaired stress responses. However, little is known about the mechanisms regulating the PRMT5 activity. Here, we report that NO positively regulates the PRMT5 activity through S-nitrosylation at Cys-125 during stress responses...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28751196/discovery-of-spiro-indole-3-2-pyrrolidin-2-1h-one-based-inhibitors-targeting-brr2-a-core-component-of-the-u5-snrnp
#19
Masahiro Ito, Misa Iwatani, Takeshi Yamamoto, Toshio Tanaka, Tomohiro Kawamoto, Daisuke Morishita, Atsushi Nakanishi, Hironobu Maezaki
Bad response to refrigeration 2 (Brr2) is a member of the Ski2-like RNA helicases, and an essential component of the U5 small nuclear ribonucleoprotein (snRNP). A particularly important role of Brr2 is the ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step in spliceosomal activation. Despite its biological importance, selective inhibitor for Brr2 had not been reported until our recent report. Here, we describe novel and structurally distinct spiro[indole-3,2'-pyrrolidin]-2(1H)-one based Brr2 inhibitors with superior activity to the previously reported 4,6-dihydropyrido[4,3-d]pyrimidine-2,7(1H,3H)-dione series...
July 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28744787/on-the-possibility-of-an-early-evolutionary-origin-for-the-spliced-leader-trans-splicing
#20
Zuzana Krchňáková, Juraj Krajčovič, Matej Vesteg
Trans-splicing is a process by which 5'- and 3'-ends of two pre-RNA molecules transcribed from different sites of the genome can be joined together to form a single RNA molecule. The spliced leader (SL) trans-splicing is mediated by the spliceosome and it allows the replacement of 5'-end of pre-mRNA by 5'(SL)-end of SL-RNA. This form of splicing has been observed in many phylogenetically unrelated eukaryotes. Either the SL trans-splicing (SLTS) originated in the last eukaryotic common ancestor (LECA) (or even earlier) and it was lost in most eukaryotic lineages, or this mechanism of RNA processing evolved several times independently in various unrelated eukaryotic taxa...
July 25, 2017: Journal of Molecular Evolution
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