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Rna splicing

Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
Oneida Espinosa-Álvarez, Paola A Ortiz, Luciana Lima, André G Costa-Martins, Myrna G Serrano, Stephane Herder, Gregory A Buck, Erney P Camargo, Patrick B Hamilton, Jamie R Stevens, Marta M G Teixeira
Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader (SL) RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T...
March 12, 2018: International Journal for Parasitology
Ana Hernández, Paula Arbildi, Cecilia Sóñora, Natalia Del Río, Juan Martin Marques
Tissue transglutaminase is a ubiquitous and multifunctional protein that contribute to several processes such as apoptosis/survival, efferocytosis, inflammation and tissue repairing under physiological and pathological conditions. Several activities can be associated with well established functional domains; in addition, four RNA alternative splice variants have been described, characterized by sequence divergences and residues deletion at the C-terminal domains Tissue transglutaminase is recognized as the central player in the physiopathology of celiac disease mainly through calcium dependent enzymatic activities...
March 15, 2018: Scandinavian Journal of Immunology
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
Hong Zhang, Lin He, Lei Cai
RNA sequencing (RNA-seq) can not only be used to identify the expression of common or rare transcripts but also in the identification of other abnormal events, such as alternative splicing, novel transcripts, and fusion genes. In principle, RNA-seq can be carried out by almost all of the next-generation sequencing (NGS) platforms, but the libraries of different platforms are not exactly the same; each platform has its own kit to meet the special requirements of the instrument design.
2018: Methods in Molecular Biology
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
Ryuji Yamamoto, Tsuyoshi Osawa, Yusuke Sasaki, Shogo Yamamoto, Motonobu Anai, Kouji Izumi, Yoshihiro Matsumura, Juro Sakai, Hiroyuki Aburatani, Atsushi Mizokami, Tatsuhiko Kodama, Toshiya Tanaka
The non-POU domain-containing octamer binding protein p54nrb /NONO is a multifunctional nuclear protein involved in RNA splicing, processing, and transcriptional regulation of nuclear hormone receptors. Through chromosome copy number analysis via whole-exome sequencing, we revealed amplification of the chromosome Xq11.22-q21.33 locus containing the androgen receptor ( AR ) and NONO genes in androgen-independent, castration-resistant prostate cancer (CRPC)-like LNCaP-SF cells. Moreover, NONO was frequently amplified and overexpressed in patients with CRPC...
February 13, 2018: Oncotarget
Masaki Kobayashi, Douglas W Zochodne
Diabetic polyneuropathy (DPN) continues to be generally considered as a "microvascular" complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, may be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of mRNA changes related to declines in structural proteins, increases in heat shock protein (HSP), increases in the receptor for advanced glycation endproducts (RAGE), declines in growth factor signaling and other changes...
March 13, 2018: Journal of Diabetes Investigation
Allan B James, Cristiane P G Calixto, Nikoleta A Tzioutziou, Wenbin Guo, Runxuan Zhang, Craig G Simpson, Wenying Jiang, Gillian A Nimmo, John W S Brown, Hugh G Nimmo
One of the ways in which plants can respond to temperature is via alternative splicing (AS). Previous work showed that temperature changes affected the splicing of several circadian clock gene transcripts. Here we investigated the role of RNA-binding splicing factors (SFs) in temperature-sensitive alternative splicing (AS) of the clock gene LATE ELONGATED HYPOCOTYL (LHY). We characterised, in wild type plants, temperature-associated isoform switching and expression patterns for SF transcripts from a high-resolution temperature and time series RNA-seq experiment...
March 13, 2018: Plant, Cell & Environment
Hisashi Wada, Nighat Yasmin, Kiyokazu Kakugawa, Michiko Ohno-Oishi, Sebastian Nieke, Chizuko Miyamoto, Sawako Muroi, Ichiro Taniuchi
During differentiation of CD4+ CD8+ double-positive (DP) thymocytes into the CD4- CD8+ single-positive (CD8SP) thymocytes committed to the cytotoxic T cell lineage, Cd8a transcription is temporally terminated after positive selection and is subsequently reinitiated, a process known as coreceptor reversal. Despite the identification of a transcriptional enhancer in the Cd8a gene that directs reporter transgene expression specifically in CD8SP thymocytes, the molecular mechanisms controlling reactivation of the Cd8a gene are not fully understood...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jie Huang, G Patricia Casas Garcia, Matthew A Perugini, Archa Fox, Charles Bond, Mihwa Lee
Members of the Drosophila Behavior Human Splicing (DBHS) protein family are nuclear proteins implicated in many layers of nuclear functions, including RNA biogenesis as well as DNA repair. Definitive of the DBHS protein family, the conserved DBHS domain provides a dimerization platform that is critical for the structural integrity and function of these proteins. The three human DBHS proteins - splicing factor proline- and glutamine-rich (SFPQ), paraspeckle component 1 (PSPC1), and non-POU domain-containing octamer binding protein (NONO) - form either homo- or heterodimers; however, the relative affinity and mechanistic details of preferential heterodimerization are yet to be deciphered...
March 12, 2018: Journal of Biological Chemistry
Yves Mugabo, Mina Sadeghi, Nancy N Fang, Thibault Mayor, Gareth E Lim
Adipogenesis involves a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, facilitate such organization, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it, but this possibility has not yet been tested. Herein, we generated mouse embryonic fibroblasts from mice overexpressing a TAP-epitope-tagged 14-3-3ζ molecule...
March 12, 2018: Journal of Biological Chemistry
Camille Ribeyre, Federico Carlini, Céline René, François Jordier, Christophe Picard, Jacques Chiaroni, Laurent Abi-Rached, Philippe Gouret, Grégory Marin, Nicolas Molinari, Pascal Chanez, Julien Paganini, Delphine Gras, Julie Di Cristofaro
Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC). Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation...
2018: Frontiers in Immunology
Christina Zarouchlioti, Beatriz Sanchez-Pintado, Nathaniel J Hafford Tear, Pontus Klein, Petra Liskova, Kalyan Dulla, Ma'ayan Semo, Anthony A Vugler, Kirithika Muthusamy, Lubica Dudakova, Hannah J Levis, Pavlina Skalicka, Pirro Hysi, Michael E Cheetham, Stephen J Tuft, Peter Adamson, Alison J Hardcastle, Alice E Davidson
Fuchs endothelial corneal dystrophy (FECD) is a common disease for which corneal transplantation is the only treatment option in advanced stages, and alternative treatment strategies are urgently required. Expansion (≥50 copies) of a non-coding trinucleotide repeat in TCF4 confers >76-fold risk for FECD in our large cohort of affected individuals. An FECD subject-derived corneal endothelial cell (CEC) model was developed to probe disease mechanism and investigate therapeutic approaches. The CEC model demonstrated that the repeat expansion leads to nuclear RNA foci, with the sequestration of splicing factor proteins (MBNL1 and MBNL2) to the foci and altered mRNA processing...
March 1, 2018: American Journal of Human Genetics
Ke Chen, Yuxuan Wang, Jie Sun
The Alu-element plays important roles in mediating alternative splicing, RNA editing and translation regulation. However, the distribution and function of the Alu-element are never analysed at the transcriptome level. This study presents a statistical analysis of the Alu-element on human transcriptome. We found that mRNAs and lncRNAs share the same sequence form for the Alu-element. The Alu-element covers 5.8% of the coding transcripts and 17.1% of the coding genes for mRNAs, and covers 9.3% of the transcripts and 13...
March 7, 2018: Biochemical and Biophysical Research Communications
Marina E Borisova, Andrea Voigt, Maxim A X Tollenaere, Sanjeeb Kumar Sahu, Thomas Juretschke, Nastasja Kreim, Niels Mailand, Chunaram Choudhary, Simon Bekker-Jensen, Masato Akutsu, Sebastian A Wagner, Petra Beli
Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway...
March 9, 2018: Nature Communications
E M Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways)...
April 2018: Medical Hypotheses
Havva Keskin, Francesca Storici
A double-strand break (DSB) is one of the most dangerous DNA lesion, and its repair is crucial for genome stability. Homologous recombination is considered the safest way to repair a DNA DSB and requires an identical or nearly identical DNA template, such as a sister chromatid or a homologous chromosome for accurate repair. Can transcript RNA serve as donor template for DSB repair? Here, we describe an approach that we developed to detect and study DNA repair by transcript RNA. Key features of the method are: (i) use of antisense (noncoding) RNA as template for DSB repair by RNA, (ii) use of intron splicing to distinguish the sequence of the RNA template from that of the DNA that generates the RNA template, and (iii) use of a trans and cis system to study how RNA repairs a DSB in homologous but distant DNA or in its own DNA, respectively...
2018: Methods in Enzymology
Yonatan Perez, Shay Menascu, Idan Cohen, Rotem Kadir, Omer Basha, Zamir Shorer, Hila Romi, Gal Meiri, Tatiana Rabinski, Rivka Ofir, Esti Yeger-Lotem, Ohad S Birk
RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts...
March 7, 2018: Brain: a Journal of Neurology
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