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https://www.readbyqxmd.com/read/29048531/origin-and-spread-of-spliceosomal-introns-insights-from-the-fungal-clade-zymoseptoria
#1
Baojun Wu, Allison I Macielog, Weilong Hao
Spliceosomal introns are a key feature of eukaryote genome architecture and have been proposed to originate from selfish group II introns from an endosymbiotic bacterium, that is, the ancestor of mitochondria. However, the mechanisms underlying the wide spread of spliceosomal introns across eukaryotic genomes have been obscure. In this study, we characterize the dynamic evolution of spliceosomal introns in the fungal genus Zymoseptoria at different evolutionary scales, that is, within a genome, among conspecific strains within species, and between different species...
October 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29048444/substoichiometric-ribose-methylations-in-spliceosomal-snrnas
#2
Nicolai Krogh, Martin Kongsbak-Wismann, Carsten Geisler, Henrik Nielsen
Sequencing-based profiling of ribose methylations is a new approach that allows for experiments addressing dynamic changes on a large scale. Here, we apply such a method to spliceosomal snRNAs present in human whole cell RNA. Analysis of solid tissue samples confirmed all previously known sites and demonstrated close to full methylation at almost all sites. Methylation changes were revealed in biological experimental settings, using T cell activation as an example, and in the T cell leukemia model, Jurkat cells...
October 19, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29046814/emergence-and-loss-of-spliceosomal-twin-introns
#3
Michel Flipphi, Norbert Ág, Levente Karaffa, Napsugár Kavalecz, Gustavo Cerqueira, Claudio Scazzocchio, Erzsébet Fekete
BACKGROUND: In the primary transcript of nuclear genes, coding sequences-exons-usually alternate with non-coding sequences-introns. In the evolution of spliceosomal intron-exon structure, extant intron positions can be abandoned and new intron positions can be occupied. Spliceosomal twin introns ("stwintrons") are unconventional intervening sequences where a standard "internal" intron interrupts a canonical splicing motif of a second, "external" intron. The availability of genome sequences of more than a thousand species of fungi provides a unique opportunity to study spliceosomal intron evolution throughout a whole kingdom by means of molecular phylogenetics...
2017: Fungal Biology and Biotechnology
https://www.readbyqxmd.com/read/29037818/snrnp-proteins-in-health-and-disease
#4
REVIEW
Michaela Krausová, David Staněk
Split gene architecture of most human genes requires removal of intervening sequences by mRNA splicing that occurs on large multiprotein complexes called spliceosomes. Mutations compromising several spliceosomal components have been recorded in degenerative syndromes and haematological neoplasia, thereby highlighting the importance of accurate splicing execution in homeostasis of assorted adult tissues. Moreover, insufficient splicing underlies defective development of craniofacial skeleton and upper extremities...
October 13, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29030393/fanconi-anemia-fancd2-and-fanci-proteins-regulate-the-nuclear-dynamics-of-splicing-factors
#5
María Moriel-Carretero, Sara Ovejero, Marie Gérus-Durand, Dimos Vryzas, Angelos Constantinou
Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the maintenance of chromosomal stability during DNA replication. FA proteins regulate replication dynamics, coordinate replication-coupled repair of interstrand DNA cross-links, and mitigate conflicts between replication and transcription. Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic cells...
October 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29023197/mutational-landscape-of-rna-binding-proteins-in-human-cancers
#6
Yaseswini Neelamraju, Abel Gonzalez-Perez, Poornima Bhat-Nakshatri, Harikrishna Nakshatri, Sarath Chandra Janga
RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations...
October 12, 2017: RNA Biology
https://www.readbyqxmd.com/read/29020945/dehydration-induced-transcriptomic-responses-in-two-tibetan-hulless-barley-hordeum-vulgare-var-nudum-accessions-distinguished-by-drought-tolerance
#7
Junjun Liang, Xin Chen, Guangbing Deng, Zhifen Pan, Haili Zhang, Qiao Li, Kaijun Yang, Hai Long, Maoqun Yu
BACKGROUND: The harsh environment on the Qinghai-Tibetan Plateau gives Tibetan hulless barley (Hordeum vulgare var. nudum) great ability to resist adversities such as drought, salinity, and low temperature, and makes it a good subject for the analysis of drought tolerance mechanism. To elucidate the specific gene networks and pathways that contribute to its drought tolerance, and for identifying new candidate genes for breeding purposes, we performed a transcriptomic analysis using two accessions of Tibetan hulless barley, namely Z772 (drought-tolerant) and Z013 (drought-sensitive)...
October 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29020934/transcriptome-analyses-reveal-sr45-to-be-a-neutral-splicing-regulator-and-a-suppressor-of-innate-immunity-in-arabidopsis-thaliana
#8
Xiao-Ning Zhang, Yifei Shi, Jordan J Powers, Nikhil B Gowda, Chong Zhang, Heba M M Ibrahim, Hannah B Ball, Samuel L Chen, Hua Lu, Stephen M Mount
BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction...
October 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28993438/architecture-and-distribution-of-introns-in-core-genes-of-four-fusarium%C3%A2-species
#9
M M Phasha, B D Wingfield, M P A Coetzee, Q C Santana, G Fourie, E T Steenkamp
Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs) has increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus...
October 9, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28986033/splicing-factor-mutations-in-the-myelodysplastic-syndromes-target-genes-and-therapeutic-approaches
#10
REVIEW
Richard N Armstrong, Violetta Steeples, Shalini Singh, Andrea Sanchi, Jacqueline Boultwood, Andrea Pellagatti
Mutations in splicing factor genes (SF3B1, SRSF2, U2AF1 and ZRSR2) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology...
September 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28985478/alteration-of-rna-splicing-by-small-molecule-inhibitors-of-the-interaction-between-nhp2l1-and-u4
#11
Barthelemy Diouf, Wenwei Lin, Asli Goktug, Christy R R Grace, Michael Brett Waddell, Ju Bao, Youming Shao, Richard J Heath, Jie J Zheng, Anang A Shelat, Mary V Relling, Taosheng Chen, William E Evans
Splicing is an important eukaryotic mechanism for expanding the transcriptome and proteome, influencing a number of biological processes. Understanding its regulation and identifying small molecules that modulate this process remain a challenge. We developed an assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to detect the interaction between the protein NHP2L1 and U4 RNA, which are two key components of the spliceosome. We used this assay to identify small molecules that interfere with this interaction in a high-throughput screening (HTS) campaign...
October 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28984182/identification-of-genome-wide-non-canonical-spliced-regions-and-analysis-of-biological-functions-for-spliced-sequences-using-read-split-fly
#12
Yongsheng Bai, Jeff Kinne, Lizhong Ding, Ethan C Rath, Aaron Cox, Siva Dharman Naidu
BACKGROUND: It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read-Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm...
October 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28984054/rna-uridylation-a-key-posttranscriptional-modification-shaping-the-coding-and-noncoding-transcriptome
#13
REVIEW
Caroline De Almeida, Hélène Scheer, Hélène Zuber, Dominique Gagliardi
RNA uridylation is a potent and widespread posttranscriptional regulator of gene expression. RNA uridylation has been detected in a range of eukaryotes including trypanosomes, animals, plants, and fungi, but with the noticeable exception of budding yeast. Virtually all classes of eukaryotic RNAs can be uridylated and uridylation can also tag viral RNAs. The untemplated addition of a few uridines at the 3' end of a transcript can have a decisive impact on RNA's fate. In rare instances, uridylation is an intrinsic step in the maturation of noncoding RNAs like for the U6 spliceosomal RNA or mitochondrial guide RNAs in trypanosomes...
October 5, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28981077/cryo-electron-microscopy-snapshots-of-the-spliceosome-structural-insights-into-a-dynamic-ribonucleoprotein-machine
#14
REVIEW
Sebastian M Fica, Kiyoshi Nagai
The spliceosome excises introns from pre-messenger RNAs using an RNA-based active site that is cradled by a dynamic protein scaffold. A recent revolution in cryo-electron microscopy (cryo-EM) has led to near-atomic-resolution structures of key spliceosome complexes that provide insight into the mechanism of activation, splice site positioning, catalysis, protein rearrangements and ATPase-mediated dynamics of the active site. The cryo-EM structures rationalize decades of observations from genetic and biochemical studies and provide a molecular framework for future functional studies...
October 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28978835/effect-of-mutation-on-diagnosis-risk-stratification-and-treatment-decisions-in-philadelphia-negative-myeloproliferative-neoplasms
#15
Keita Kirito
Since the discovery of the activating mutation of JAK2, known as JAK2V617F, our understanding of mutation profiles, and the biological significance of this mutation in Philadelphia-negative (Ph-) MPNs has drastically changed over the last decade. Mutations of the thrombopoietin receptor MPL and chaperone protein calreticulin gene also induce aberrant activation of JAK and downstream molecules, including STAT proteins, and contribute to the development of MPNs. Mutations of the genes JAK2, MPL, and calreticulin are referred to as "driver mutations" for MPNs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978087/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#16
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977850/integrated-transcriptomic-analysis-of-distance-related-field-cancerization-in-rectal-cancer-patients
#17
Honglin Guo, Weigen Zeng, Lin Feng, Xuexin Yu, Ping Li, Kaitai Zhang, Zhixiang Zhou, Shujun Cheng
Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974555/orchestrated-positioning-of-post-transcriptional-modifications-at-the-branch-point-recognition-region-of-u2-snrna
#18
Svetlana Deryusheva, Joseph G Gall
The branch point recognition region of spliceosomal snRNA U2 is heavily modified post-transcriptionally in most eukaryotic species. We focused on this region to learn how nearby positions may interfere with each other when targeted for modification. Using an in vivo yeast Saccharomyces cerevisiae cell system we tested modification activity of several guide RNAs from human, mouse, the frog Xenopus tropicalis, the fruit fly Drosophila melanogaster and the worm Caenorhabditis elegans. We experimentally verified predictions for vertebrate U2 modification guide RNAs SCARNA4 and SCARNA15, and identified a C...
September 29, 2017: RNA
https://www.readbyqxmd.com/read/28966666/identification-of-potential-therapeutic-target-genes-and-mirnas-for-primary-myelofibrosis-with-microarray-analysis
#19
Yong Liu, Bo Wei, Xuebing Zhang, Dehui Xu, Bo Wang, Guochao Yin, Dawer Gu, Yuxiang Li, Daliang Kong
The aim of the present study was to identify potential therapeutic target genes and miRNAs for primary myelofibrosis (PMF). The dataset GSE53482 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) of peripheral blood (PB) cluster of differentiation (CD)34(+) cells from PMF patients (PB-PMF group) and peripheral blood CD34(+) cells from healthy individuals (PB-control group) were analyzed using the Linear Models for Microarray Data package in R...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28965864/minor-spliceosome-and-disease
#20
REVIEW
Bhupendra Verma, Maureen V Akinyi, Antto J Norppa, Mikko J Frilander
The U12-type dependent (minor) spliceosome excises a rare group of introns that are characterized by a highly conserved 5' splice site and branch point sequence. Several new congenital or somatic diseases have recently been associated with mutations in components of the minor spliceosome. A common theme in these diseases is the detection of elevated levels of transcripts containing U12-type introns, of which a subset is associated with other splicing defects. Here we review the present understanding of the minor spliceosome diseases, particularly those associated with the specific components of the minor spliceosome...
September 28, 2017: Seminars in Cell & Developmental Biology
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