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Rna splicing

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https://www.readbyqxmd.com/read/28231281/the-intron-in-centromeric-noncoding-rna-facilitates-rnai-mediated-formation-of-heterochromatin
#1
Masatoshi Mutazono, Misato Morita, Chihiro Tsukahara, Madoka Chinen, Shiori Nishioka, Tatsuhiro Yumikake, Kohei Dohke, Misuzu Sakamoto, Takashi Ideue, Jun-Ichi Nakayama, Kojiro Ishii, Tokio Tani
In fission yeast, the formation of centromeric heterochromatin is induced through the RNA interference (RNAi)-mediated pathway. Some pre-mRNA splicing mutants (prp) exhibit defective formation of centromeric heterochromatin, suggesting that splicing factors play roles in the formation of heterochromatin, or alternatively that the defect is caused by impaired splicing of pre-mRNAs encoding RNAi factors. Herein, we demonstrate that the splicing factor spPrp16p is enriched at the centromere, and associates with Cid12p (a factor in the RNAi pathway) and the intron-containing dg ncRNA...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28223408/inducing-circular-rna-formation-using-the-crispr-endoribonuclease-csy4
#2
Erin K Borchardt, Rita M Meganck, Heather A Vincent, Christopher B Ball, Silvia B V Ramos, Nathaniel J Moorman, William F Marzluff, Aravind Asokan
Circular RNAs (circRNAs) are highly stable, covalently closed RNAs that are regulated in a spatiotemporal manner and whose functions are largely unknown. These molecules have the potential to be incorporated into engineered systems with broad technological implications. Here we describe a switch for inducing backsplicing of an engineered circRNA that relies on the CRISPR endoribonuclease, Csy4, as an activator of circularization. The endoribonuclease activity and 3' end-stabilizing properties of Csy4 are particularly suited for this task...
February 21, 2017: RNA
https://www.readbyqxmd.com/read/28223400/distal-cpg-islands-can-serve-as-alternative-promoters-to-transcribe-genes-with-silenced-proximal-promoters
#3
Shrutii Sarda, Avinash Das, Charles Vinson, Sridhar Hannenhalli
DNA methylation at the promoter of a gene is presumed to render it silent, yet, a sizable fraction of genes with methylated proximal-promoters exhibit elevated expression. Here, we show, through extensive analysis of the methylome and transcriptome in 34 tissues, that in many such cases, transcription is initiated by a distal upstream CpG island (CGI) located several kilobases away that functions as an alternative promoter. Specifically, such genes are expressed precisely when the neighboring CGI remains unmethylated, but remain silenced otherwise...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28223366/la-deletion-from-mouse-brain-alters-pre-trna-metabolism-and-accumulation-of-pre-5-8s-rrna-with-neuron-death-and-reactive-astrocytosis
#4
Nathan H Blewett, James R Iben, Sergei Gaidamakov, Richard J Maraia
Human La antigen (Sjögren's syndrome antigen B, SSB) is an abundant multifunctional RNA-binding protein. In the nucleoplasm, La binds to and protects from 3' exonucleases, the ends of precursor-tRNAs and other transcripts synthesized by RNA polymerase III, and facilitates their maturation, while a nucleolar isoform has been implicated in rRNA biogenesis by multiple independent lines of evidence. We showed earlier that conditional La knockout (La cKO) from mouse cortex neurons results in defective tRNA processing although pathway(s) involved in neuronal loss thereafter was unknown...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223317/stabilized1-modulates-pre-mrna-splicing-for-thermotolerance
#5
Geundon Kim, Young-Hee Cho, Byeong-Ha Lee, Sang-Dong Yoo
High temperature stress often leads to differential RNA splicing, thus accumulating different types and/or amounts of mature mRNAs in eukaryotic cells. However, regulatory mechanisms underlying plant pre-mRNA splicing in the environmental stress conditions remain elusive. Herein, we describe that a U5-snRNP-interacting protein homolog STABILIZED1 (STA1) has pre-mRNA splicing activity for heat-inducible transcripts including HEAT STRESS TRANSCRIPTION FACTORS and various HEAT SHOCK PROTEINS for the establishment of heat stress tolerance in Arabidopsis thaliana...
February 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28223168/prognostic-alternative-mrna-splicing-signature-in-non-small-cell-lung-cancer
#6
Yuan Li, Nan Sun, Zhiliang Lu, Shouguo Sun, Jianbing Huang, Zhaoli Chen, Jie He
Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. Genome-wide alternative splicing profiling in lung cancer remains largely unstudied. We generated alternative splicing profiles in 491 lung adenocarcinoma (LUAD) and 471 lung squamous cell carcinoma (LUSC) patients in TCGA using RNA-seq data, prognostic models and splicing networks were built by integrated bioinformatics analysis. A total of 3691 and 2403 alternative splicing events were significantly associated with patient survival in LUAD and LUSC, respectively, including EGFR, CD44, PIK3C3, RRAS2, MAPKAP1 and FGFR2...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28222683/manananggal-a-novel-viewer-for-alternative-splicing-events
#7
Matthias Barann, Ralf Zimmer, Fabian Birzele
BACKGROUND: Alternative splicing is an important cellular mechanism that can be analyzed by RNA sequencing. However, identification of splicing events in an automated fashion is error-prone. Thus, further validation is required to select reliable instances of alternative splicing events (ASEs). There are only few tools specifically designed for interactive inspection of ASEs and available visualization approaches can be significantly improved. RESULTS: Here, we present Manananggal, an application specifically designed for the identification of splicing events in next generation sequencing data...
February 21, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28221306/whole-exome-sequencing-identifies-atypical-welander-distal-myopathy-in-patient
#8
Jennifer Gass, Patrick Blackburn, Jessica Jackson, Kimberly Harris, Duygu Selcen, Elliot Dimberg, Paldeep Atwal
Welander distal myopathy is a rare autosomal dominant disorder characterized by muscle weakness in the hands and feet. Exome sequencing of affected families discovered a segregating p.Glu384Lys pathogenic variant in TIA-1 as the main genetic cause of Welander distal myopathy. TIA-1 encodes an RNA-binding protein which serves as a key component of stress granules. This protein also regulates splicing and translation of mRNA. Our patient developed progressive weakness in his hands and feet during his late 40s that was misdiagnosed as a neuropathy that caused muscle atrophy...
March 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#9
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28216641/targeted-rp9-ablation-and-mutagenesis-in-mouse-photoreceptor-cells-by-crispr-cas9
#10
Ji-Neng Lv, Gao-Hui Zhou, Xuejiao Chen, Hui Chen, Kun-Chao Wu, Lue Xiang, Xin-Lan Lei, Xiao Zhang, Rong-Han Wu, Zi-Bing Jin
Precursor messenger RNA (Pre-mRNA) splicing is an essential biological process in eukaryotic cells. Genetic mutations in many spliceosome genes confer human eye diseases. Mutations in the pre-mRNA splicing factor, RP9 (also known as PAP1), predispose autosomal dominant retinitis pigmentosa (adRP) with an early onset and severe vision loss. However, underlying molecular mechanisms of the RP9 mutation causing photoreceptor degeneration remains fully unknown. Here, we utilize the CRISPR/Cas9 system to generate both the Rp9 gene knockout (KO) and point mutation knock in (KI) (Rp9, c...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#11
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213128/quantitative-proteomic-analysis-of-human-testis-reveals-system-wide-molecular-and-cellular-pathways-associated-with-non-obstructive-azoospermia
#12
Mehdi Alikhani, Mehdi Mirzaei, Marjan Sabbaghian, Pouria Parsamatin, Razieh Karamzadeh, Samane Adib, Niloofar Sodeifi, Mohammad Ali Sadighi Gilani, Masoud Zabet-Moghaddam, Lindsay Parker, Yunqi Wu, Vivek Gupta, Paul A Haynes, Hamid Gourabi, Hossein Baharvand, Ghasem Hosseini Salekdeh
: Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS)...
February 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28211799/increased-expression-of-long-non-coding-rna-glidr-in-prostate-cancer
#13
Yingyi Zhang, Zhe Kong, Yalong Zhang, Wenhua Huang, Hai Wu, Xuechao Wan, Yao Li
Prostate cancer (PCa) was one of the most common cancers in males in China. Long non-coding RNAs (lncRNA), a class of non-coding RNAs with more than 200 nucleotides, played key roles in the progression of prostate cancer. GLIDR, a novel long intergenic ncRNA, was found to be upregulated in tumors compared to normal tissues by using publically databases. In the clinical validation cohort, our results showed GLIDR was significantly up-regulated in prostate cancer samples and cell lines. To explore the potential functions of the GLIDR, we constructed gene co-expression networks and applied GO analysis...
February 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28209301/iswi-atp-dependent-remodeling-of-nucleoplasmic-%C3%AF-speckles-in-the-brain-of-drosophila-melanogaster
#14
Luca Lo Piccolo, Andrea Attardi, Rosa Bonaccorso, Lorenzo Li Greci, Giorgio Giurato, Antonia Maria Rita Ingrassia, Maria Cristina Onorati
Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs. These proteins participate in every step of mRNA cycle, such as mRNA export, localization, translation, stability and alternative splicing. At least 14 major hnRNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hnRNPs are known to be nucleus-localized and associated with the long non-coding RNA (lncRNA) heat shock responsive ω (hsrω) in the omega speckle compartments (ω-speckles)...
December 22, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28208770/splicing-and-polyadenylation-of-human-papillomavirus-type-16-mrnas
#15
REVIEW
Chengjun Wu, Naoko Kajitani, Stefan Schwartz
The human papillomavirus type 16 (HPV16) life cycle can be divided into an early stage in which the HPV16 genomic DNA is replicated, and a late stage in which the HPV16 structural proteins are synthesized and virions are produced. A strong coupling between the viral life cycle and the differentiation state of the infected cell is highly characteristic of all HPVs. The switch from the HPV16 early gene expression program to the late requires a promoter switch, a polyadenylation signal switch and a shift in alternative splicing...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208661/differential-binding-of-three-major-human-adar-isoforms-to-coding-and-long-non-coding-transcripts
#16
Josephine Galipon, Rintaro Ishii, Yutaka Suzuki, Masaru Tomita, Kumiko Ui-Tei
RNA editing by deamination of adenosine to inosine is an evolutionarily conserved process involved in many cellular pathways, from alternative splicing to miRNA targeting. In humans, it is carried out by no less than three major adenosine deaminases acting on RNA (ADARs): ADAR1-p150, ADAR1-p110, and ADAR2. However, the first two derive from alternative splicing, so that it is currently impossible to delete ADAR1-p110 without also knocking out ADAR1-p150 expression. Furthermore, the expression levels of ADARs varies wildly among cell types, and no study has systematically explored the effect of each of these isoforms on the cell transcriptome...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28205459/effects-of-an-antagonistic-analog-of-growth-hormone-releasing-hormone-on-endometriosis-in-a-mouse-model-and-in-vitro
#17
Frank Köster, Li Jin, Yuanming Shen, Andrew V Schally, Ren-Zhi Cai, Norman L Block, Daniela Hornung, Gabriele Marschner, Achim Rody, Jörg B Engel, Dominique Finas
Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28205408/rna-processing-and-protein-expression-of-hla-b-07-44n
#18
A Balas, F García-Sánchez, J L Vicario
BACKGROUND: The assignment of human leukocyte antigen (HLA) null alleles is clinically relevant in the setting of stem cell transplantation. Cell surface expression profiling and mRNA processing analysis of the HLA-B allele previously designated as B*07:44, have been performed. MATERIALS AND METHODS: Cell surface expression of HLA-B*07:44 was determined using flow cytometry. Genomic full-length and HLA-B*07-specific cDNA sequencing were carried out by Sanger procedure...
February 15, 2017: HLA
https://www.readbyqxmd.com/read/28202761/the-long-noncoding-rna-neat1-exerts-anti-hantaviral-effects-by-acting-as-a-positive-feedback-for-rig-i-signaling
#19
Hongwei Ma, Peijun Han, Wei Ye, Hesong Chen, Xuyang Zheng, Linfeng Cheng, Liang Zhang, Lan Yu, Xing'an Wu, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA, NEAT1, as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202748/rna-splicing-in-human-disease-and-in-the-clinic
#20
REVIEW
Diana Baralle, Emanuele Buratti
Defects at the level of the pre-mRNA splicing process represent a major cause of human disease. Approximately 15-50% of all human disease mutations have been shown to alter functioning of basic and auxiliary splicing elements. These elements are required to ensure proper processing of pre-mRNA splicing molecules, with their disruption leading to misprocessing of the pre-mRNA molecule and disease. The splicing process is a complex process, with much still to be uncovered before we are able to accurately predict whether a reported genomic sequence variant (GV) represents a splicing-associated disease mutation or a harmless polymorphism...
March 1, 2017: Clinical Science (1979-)
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