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Alternative splicing

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https://www.readbyqxmd.com/read/28334977/sclip-an-integrated-platform-to-study-rna-protein-interactomes-in-biomedical-research-identification-of-cstf2tau-in-alternative-processing-of-small-nuclear-rnas
#1
Yulia Kargapolova, Michal Levin, Karl Lackner, Sven Danckwardt
RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here, we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334903/n6-methyladenosine-alters-rna-structure-to-regulate-binding-of-a-low-complexity-protein
#2
Nian Liu, Katherine I Zhou, Marc Parisien, Qing Dai, Luda Diatchenko, Tao Pan
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#3
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334849/icf-specific-dnmt3b-dysfunction-interferes-with-intragenic-regulation-of-mrna-transcription-and-alternative-splicing
#4
Sole Gatto, Miriam Gagliardi, Monica Franzese, Sylwia Leppert, Mariarosaria Papa, Marco Cammisa, Giacomo Grillo, Guillame Velasco, Claire Francastel, Shir Toubiana, Maurizio D'Esposito, Claudia Angelini, Maria R Matarazzo
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown...
March 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334819/comparative-analyses-of-the-thermodynamic-rna-binding-signatures-of-different-types-of-rna-recognition-motifs
#5
Brighton Samatanga, Antoine Cléry, Pierre Barraud, Frédéric H-T Allain, Ilian Jelesarov
RNA recognition motifs (RRMs) are structurally versatile domains important in regulation of alternative splicing. Structural mechanisms of sequence-specific recognition of single-stranded RNAs (ssRNAs) by RRMs are well understood. The thermodynamic strategies are however unclear. Therefore, we utilized microcalorimetry and semi-empirical analyses to comparatively analyze the cognate ssRNA binding thermodynamics of four different RRM domains, each with a different RNA binding mode. The different binding modes are: canonical binding to the β-sheet surface; canonical binding with involvement of N- and C-termini; binding to conserved loops; and binding to an α-helix...
February 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334781/auf1-facilitates-microrna-mediated-gene-silencing
#6
Kyung-Won Min, Myung Hyun Jo, Soochul Shin, Sylvia Davila, Richard W Zealy, Soo Im Kang, Lawson T Lloyd, Sungchul Hohng, Je-Hyun Yoon
Eukaryotic mRNA decay is tightly modulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs). RBP AU-binding factor 1 (AUF1) has four isoforms resulting from alternative splicing and is critical for miRNA-mediated gene silencing with a distinct preference of target miRNAs. Previously, we have shown that AUF1 facilitates miRNA loading to Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex. Here, we further demonstrate that depletion of AUF1 abolishes the global interaction of miRNAs and AGO2...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334074/genome-wide-analysis-reveals-that-exon-methylation-facilitates-its-selective-usage-in-the-human-transcriptome
#7
Shengli Li, Jiwei Zhang, Shenglin Huang, Xianghuo He
DNA methylation, especially in promoter regions, is a well-characterized epigenetic marker related to gene expression regulation in eukaryotes. However, the role of intragenic DNA methylation in the usage of corresponding exons still remains elusive. In this study, we described the DNA methylome across 10 human tissues. The human genome showed both conserved and varied methylation levels among these tissues. We found that the methylation densities in promoters and first exons were negatively correlated with the corresponding gene expression level...
February 16, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28332713/the-mitochondrial-pentatricopeptide-repeat-protein-ppr19-is-involved-in-the-stabilization-of-nadh-dehydrogenase-1-transcripts-and-is-crucial-for-mitochondrial-function-and-arabidopsis-thaliana-development
#8
Kwanuk Lee, Ji Hoon Han, Youn-Il Park, Catherine Colas des Francs-Small, Ian Small, Hunseung Kang
Despite the importance of pentatricopeptide repeat (PPR) proteins in organellar RNA metabolism and plant development, the functions of many PPR proteins remain unknown. Here, we determined the role of a mitochondrial PPR protein (At1g52620) comprising 19 PPR motifs, thus named PPR19, in Arabidopsis thaliana. The ppr19 mutant displayed abnormal seed development, reduced seed yield, delayed seed germination, and retarded growth, indicating that PPR19 is indispensable for normal growth and development of Arabidopsis thaliana...
March 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/28331370/can-the-hiv-1-splicing-machinery-be-targeted-for-drug-discovery
#9
REVIEW
Zodwa Dlamini, Rodney Hull
HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages of viral development, and this is achieved through the control of alternative splicing and the export of these transcripts from the nucleus. The nuclear export is controlled by the HIV protein Rev being required to transport incompletely spliced and partially spliced mRNA from the nucleus where they are normally retained. This implies a close relationship between the control of alternate splicing and the nuclear export of mRNA in the control of HIV-1 viral proliferation...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/28331096/comprehensive-transcriptome-analyses-reveal-that-potato-spindle-tuber-viroid-triggers-genome-wide-changes-in-alternative-splicing-inducible-trans-acting-activity-of-phasirnas-and-immune-responses
#10
Yi Zheng, Ying Wang, Biao Ding, Zhangjun Fei
Many pathogens express non-coding RNAs (ncRNAs) during infection processes. In the most extreme case, pathogenic ncRNAs alone (such as viroids) can infect eukaryotic organisms leading to diseases. While a few of pathogenic ncRNAs have been implicated in regulating gene expression, functions of most pathogenic ncRNAs in host-pathogen interactions remain unclear. Here we employ potato spindle tuber viroid (PSTVd)-infecting tomato as a system to dissect host interactions with pathogenic ncRNAs, using comprehensive transcriptome analyses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330560/an-event-of-alternative-splicing-affects-the-expression-of-the-ntrc-gene-encoding-nadph-thioredoxin-reductase-c-in-seed-plants
#11
Victoria A Nájera, María Cruz González, Juan Manuel Pérez-Ruiz, Francisco Javier Cejudo
The NTRC gene encodes a NADPH-dependent thioredoxin reductase with a joint thioredoxin domain, exclusive of photosynthetic organisms. An updated search shows that although most species harbor a single copy of the NTRC gene, two copies were identified in different species of the genus Solanum, Glycine max and the moss Physcomitrella patens. The phylogenetic analysis of NTRCs from different sources produced a tree with the major groups of photosynthetic organisms: cyanobacteria, algae and land plants, indicating the evolutionary success of the NTRC gene among photosynthetic eukaryotes...
May 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28330331/identification-and-quantification-of-novel-rna-isoforms-in-horn-cancer-of-bos-indicus-by-comprehensive-rna-seq
#12
Subhash J Jakhesara, Prakash G Koringa, Neelam M Nathani, Chaitanya G Joshi
Horn cancer (HC) is a squamous cell carcinoma of horn, commonly observed in Bos indicus of the Asian countries. To elucidate the complexity of alternative splicing present in the HC, high-throughput sequencing and analysis of HC and matching horn normal (HN) tissue were carried out. A total of 535,067 and 849,077 reads were analysed after stringent quality filtering for HN and HC, respectively. Cufflinks pipeline for transcriptome analysis revealed 4786 novel splice isoforms comprising 2432 exclusively in HC, 2055 exclusively in HN and 298 in both the conditions...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329680/major-roles-for-pyrimidine-dimers-nucleotide-excision-repair-and-atr-in-the-alternative-splicing-response-to-uv-irradiation
#13
Manuel J Muñoz, Nicolás Nieto Moreno, Luciana E Giono, Adrián E Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-Méndez, Carlos F M Menck, Benjamin J Blencowe, Manuel Irimia, Marco Foiani, Alberto R Kornblihtt
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28326306/cd44-a-multifunctional-cell-surface-adhesion-receptor-is-a-regulator-of-progression-and-metastasis-of-cancer-cells
#14
REVIEW
Linda T Senbanjo, Meenakshi A Chellaiah
CD44 is a cell surface adhesion receptor that is highly expressed in many cancers and regulates metastasis via recruitment of CD44 to the cell surface. Its interaction with appropriate extracellular matrix ligands promotes the migration and invasion processes involved in metastases. It was originally identified as a receptor for hyaluronan or hyaluronic acid and later to several other ligands including, osteopontin (OPN), collagens, and matrix metalloproteinases. CD44 has also been identified as a marker for stem cells of several types...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28325281/systemic-antisense-therapeutics-for-dystrophin-and-myostatin-exon-splice-modulation-improve-muscle-pathology-of-adult-mdx-mice
#15
Ngoc Lu-Nguyen, Alberto Malerba, Linda Popplewell, Fred Schnell, Gunnar Hanson, George Dickson
Antisense-mediated exon skipping is a promising approach for the treatment of Duchenne muscular dystrophy (DMD), a rare life-threatening genetic disease due to dystrophin deficiency. Such an approach can restore the disrupted reading frame of dystrophin pre-mRNA, generating a truncated form of the protein. Alternatively, antisense therapy can be used to induce destructive exon skipping of myostatin pre-mRNA, knocking down myostatin expression to enhance muscle strength and reduce fibrosis. We have reported previously that intramuscular or intraperitoneal antisense administration inducing dual exon skipping of dystrophin and myostatin pre-mRNAs was beneficial in mdx mice, a mouse model of DMD, although therapeutic effects were muscle type restricted, possibly due to the delivery routes used...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324984/prediction-method-for-intronic-alternative-polyadenylation-sites
#16
Shanxin Zhang
Alternative Polyadenylation (APA) of mRNAs has been proven as a considerable mechanism for post-transcriptional gene regulation. The interplay between Intronic APA and splicing may affect the isoforms of mRNAs. In this paper, we have found four prevalent motifs, i.e. AATAAA, TTTTTTTT, CCAGSCTGG and RGYRYRGTGG surrounding the polyadenylation sites; then we proposed a new computational method to identify the Intronic APA sites in the human genome, which is based on a Support Vector Machine (SVM) with weighted degree string kernel...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28324222/bdnf-mrna-splice-variants-differentially-impact-ca1-and-ca3-dendrite-complexity-and-spine-morphology-in-the-hippocampus
#17
Kristen R Maynard, John W Hobbs, Mahima Sukumar, Alisha S Kardian, Dennisse V Jimenez, Robert J Schloesser, Keri Martinowich
Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin critical for neuronal plasticity in the hippocampus. BDNF is encoded by multiple transcripts with alternative 5' untranslated regions (5'UTRS) that display activity-induced targeting to distinct subcellular compartments. While individual Bdnf 5'UTR transcripts influence dendrite morphology in cultured hippocampal neurons, it is unknown whether Bdnf splice variants impact dendrite arborization in functional classes of neurons in the intact hippocampus...
March 21, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#18
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322992/activation-of-the-intronic-cryptic-5-splice-site-depends-on-its-distance-to-the-upstream-cassette-exon
#19
Wei Liu, Xia Li, Shengjie Liao, Kefeng Dou, Yi Zhang
Splice site selection is a key step that determines the mRNA isoforms generated from a single transcript. The large diversity in splice site sequences emphasizes the plasticity of splice site recognition and selection. In this report, a cell-based reporter system using a SMN1/2 cassette exon was applied to the roles governing the activation of a cryptic 5'SS from the intron 4 of the CT/CGRP gene. We found that the cryptic site was activated when placed within 124nt downstream the cassette exon, and the level of activation was negatively correlated with its distance from the exon...
March 18, 2017: Gene
https://www.readbyqxmd.com/read/28322931/the-alternatively-spliced-lrrfip1-isoform-1-is-a-key-regulator-of-the-wnt-%C3%AE-catenin-transcription-pathway
#20
Pauline Labbé, Emilie Faure, Simon Lecointe, Solena Le Scouarnec, Florence Kyndt, Marie Marrec, Thierry Le Tourneau, Bernard Offmann, Cécile Duplaà, Stéphane Zaffran, Jean Jacques Schott, Jean Merot
The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway...
March 18, 2017: Biochimica et Biophysica Acta
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