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Alternative splicing

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https://www.readbyqxmd.com/read/29351989/iterative-random-forests-to-discover-predictive-and-stable-high-order-interactions
#1
Sumanta Basu, Karl Kumbier, James B Brown, Bin Yu
Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order interactions drive gene expression presents a substantial statistical challenge. Building on random forests (RFs) and random intersection trees (RITs) and through extensive, biologically inspired simulations, we developed the iterative random forest algorithm (iRF)...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351731/a-chelicerate-specific-burst-of-nonclassical-dscam-diversity
#2
Guozheng Cao, Yang Shi, Jian Zhang, Hongru Ma, Shouqing Hou, Haiyang Dong, Weiling Hong, Shuo Chen, Hao Li, Yandan Wu, Pengjuan Guo, Xu Shao, Bingbing Xu, Feng Shi, Yijun Meng, Yongfeng Jin
BACKGROUND: The immunoglobulin (Ig) superfamily receptor Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of isoforms via alternative splicing, which is essential for both nervous and immune systems in insects. However, further information is required to develop a comprehensive view of Dscam diversification across the broad spectrum of Chelicerata clades, a basal branch of arthropods and the second largest group of terrestrial animals. RESULTS: In this study, a genome-wide comprehensive analysis of Dscam genes across Chelicerata species revealed a burst of nonclassical Dscams, categorised into four types-mDscam, sDscamα, sDscamβ, and sDscamγ-based on their size and structure...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29351555/omega-3-fatty-acid-desaturase-gene-family-from-two-%C3%AF-3-sources-salvia-hispanica-and-perilla-frutescens-cloning-characterization-and-expression
#3
Yufei Xue, Baojun Chen, Aung Naing Win, Chun Fu, Jianping Lian, Xue Liu, Rui Wang, Xingcui Zhang, Yourong Chai
Omega-3 fatty acid desaturase (ω-3 FAD, D15D) is a key enzyme for α-linolenic acid (ALA) biosynthesis. Both chia (Salvia hispanica) and perilla (Perilla frutescens) contain high levels of ALA in seeds. In this study, the ω-3 FAD gene family was systematically and comparatively cloned from chia and perilla. Perilla FAD3, FAD7, FAD8 and chia FAD7 are encoded by single-copy (but heterozygous) genes, while chia FAD3 is encoded by 2 distinct genes. Only 1 chia FAD8 sequence was isolated. In these genes, there are 1 to 6 transcription start sites, 1 to 8 poly(A) tailing sites, and 7 introns...
2018: PloS One
https://www.readbyqxmd.com/read/29351317/hafts-are-novel-lncrna-transcripts-from-aflatoxin-exposure
#4
B Alex Merrick, Justin S Chang, Dhiral P Phadke, Meredith A Bostrom, Ruchir R Shah, Xinguo Wang, Oksana Gordon, Garron M Wright
The transcriptome can reveal insights into precancer biology. We recently conducted RNA-Seq analysis on liver RNA from male rats exposed to the carcinogen, aflatoxin B1 (AFB1), for 90 days prior to liver tumor onset. Among >1,000 differentially expressed transcripts, several novel, unannotated Cufflinks-assembled transcripts, or HAfTs (Hepatic Aflatoxin Transcripts) were found. We hypothesized PCR-cloning and RACE (rapid amplification of cDNA ends) could further HAfT identification. Sanger data was obtained for 6 transcripts by PCR and 16 transcripts by 5'- and 3'-RACE...
2018: PloS One
https://www.readbyqxmd.com/read/29346776/loss-of-an-androgen-inactivating-and-isoform-specific-hsd17b4-splice-form-enables-emergence-of-castration-resistant-prostate-cancer
#5
Hyun-Kyung Ko, Michael Berk, Yoon-Mi Chung, Belinda Willard, Rohan Bareja, Mark Rubin, Andrea Sboner, Nima Sharifi
Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic mechanisms that allow sustained testosterone and/or dihydrotestosterone to stimulate progression. 17β-Hydroxysteroid dehydrogenase type 4 (17βHSD4), encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone by converting them to their respective inert 17-keto steroids. Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor prognosis. Here, we show that, of five alternative splice forms, only isoform 2 encodes an enzyme capable of testosterone and dihydrotestosterone inactivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346309/the-role-of-e6-spliced-isoforms-e6-in-human-papillomavirus-induced-carcinogenesis
#6
REVIEW
Leslie Olmedo-Nieva, J Omar Muñoz-Bello, Adriana Contreras-Paredes, Marcela Lizano
Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter. Through alternative splicing, this pre-mRNA produces a variety of E6 spliced transcripts termed E6*. In pre-malignant lesions and HPV-related cancers, different E6/E6* transcriptional patterns have been found, although they have not been clearly associated to cancer development...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29346292/isoform-sequencing-and-state-of-art-applications-for-unravelling-complexity-of-plant-transcriptomes
#7
REVIEW
Dong An, Hieu X Cao, Changsheng Li, Klaus Humbeck, Wenqin Wang
Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications...
January 18, 2018: Genes
https://www.readbyqxmd.com/read/29344170/phosphorylation-of-ser6-in-hnrnpa1-by-s6k2-regulates-glucose-metabolism-and-cell-growth-in-colorectal-cancer
#8
Yan Sun, Man Luo, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Abnormal glucose metabolism is critical in colorectal cancer (CRC) development. Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform, serves important functions in reprogramming the glucose metabolism of cancer cells. Preferential expression of PKM2 is primarily driven by alternative splicing, which is coordinated by a group of splicing factors including heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif containing. However, the underlying molecular mechanisms associated with cancer cell expression of PKM2, instead of PKM1, remain unknown...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343500/cbf%C3%AE-2-controls-differentiation-of-and-confers-homing-capacity-to-prethymic-progenitors
#9
Mari Tenno, Satoshi Kojo, Divine-Fondzenyuy Lawir, Isabell Hess, Katsuyuki Shiroguchi, Takashi Ebihara, Takaho A Endo, Sawako Muroi, Rumi Satoh, Hiroshi Kawamoto, Thomas Boehm, Ichiro Taniuchi
Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9...
January 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29343211/pax6-alternative-splicing-and-corneal-development
#10
Jung Woo Park, Juan Yang, Ren-He Xu
Paired box protein 6 (PAX6) is a master regulator of the eye development. Over the last past two decades, our understanding of eye development, especially the molecular function of PAX6, has focused on transcriptional control of the Pax6 expression. However, other regulatory mechanisms for gene expression, including alternative splicing (AS), have been understudied in the eye development. Recent findings suggest that two PAX6 isoforms generated by alternative splicing of Pax6 pre-mRNA may play previously underappreciated role(s) during eye development, especially, the corneal development...
January 17, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29340952/rfathm6a-a-new-tool-for-predicting-m6a-sites-in-arabidopsis-thaliana
#11
Xiaofeng Wang, Renxiang Yan
We curated a reliable dataset of m6A sites in Arabidopsis thaliana, built competitive models for predicting m6A sites, extracted predominant rules from the prediction models and analyzed the most important features. In biological RNA, approximately 150 chemical modifications have been discovered, of which N6-methyladenine (m6A) is the most prevalent and abundant. This modification plays an essential role in a myriad of biological mechanisms and regulates RNA localization, nuclear export, translation, stability, alternative splicing, and other processes...
January 16, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29339763/glucocorticoid-receptor-gr%C3%AE-regulates-glucocorticoid-induced-ocular-hypertension-in-mice
#12
Gaurang C Patel, Yang Liu, J Cameron Millar, Abbot F Clark
Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339533/learning-dependent-chromatin-remodeling-highlights-noncoding-regulatory-regions-linked-to-autism
#13
John N Koberstein, Shane G Poplawski, Mathieu E Wimmer, Giulia Porcari, Charlly Kao, Bruce Gomes, Davide Risso, Hakon Hakonarson, Nancy R Zhang, Robert T Schultz, Ted Abel, Lucia Peixoto
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is associated with genetic risk factors. Most human disease-associated single-nucleotide polymorphisms (SNPs) are not located in genes but rather are in regulatory regions that control gene expression. The function of regulatory regions is determined through epigenetic mechanisms. Parallels between the cellular basis of development and the formation of long-term memory have long been recognized, particularly the role of epigenetic mechanisms in both processes...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339256/the-pbii-gene-of-the-human-salivary-proline-rich-protein-p-b-produces-another-protein-q504x8-with-an-opiorphin-homolog-qrgpr
#14
Eiichi Saitoh, Takuya Sega, Akane Imai, Satoko Isemura, Tetsuo Kato, Akihito Ochiai, Masayuki Taniguchi
OBJECTIVES: The NCBI gene database and human-transcriptome database for alternative splicing were used to determine the expression of mRNAs for P-B (SMR3B) and variant form of P-B. The translational product from the former mRNA was identified as the protein named P-B, whereas that from the latter has not yet been elucidated. In the present study, we investigated the expression of P-B and its variant form at the protein level. DESIGN: To identify the variant protein of P-B, (1) cationic proteins with a higher isoelectric point in human pooled whole saliva were purified by a two dimensional liquid chromatography; (2) the peptide fragments generated from the in-solution of all proteins digested with trypsin separated and analyzed by MALDI-TOF-MS; and (3) the presence or absence of P-B in individual saliva was examined by 15% SDS-PAGE...
January 10, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29338343/molecular-analysis-of-anthocyanin-biosynthesis-pathway-genes-and-their-differential-expression-in-mango-peel
#15
Anju Bajpai, Kasim Khan, M Muthukumar, S Rajan, Nagendra Kumar Singh
Mango fruit is cherished by masses for its taste and nutrition, contributed by color, flavor and aroma. Among these, peel color is an important trait contributing to fruit quality and market value. We attempted to elucidate the role of key genes of anthocyanin biosynthesis pathway related to fruit peel color from the leaf transcriptome of cv. Amrapali. A total of 108 mined transcript sequences were assigned to phenylpropanoid flavonoid pathway from which 15 contigs representing anthocyanin biosynthesis genes were annotated...
January 16, 2018: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/29337206/evolution-of-the-pou1f1-transcription-factor-in-mammals-rapid-change-of-the-alternatively-spliced-%C3%AE-domain
#16
Michael Wallis
The POU1F1 (Pit-1) transcription factor is important in regulating expression of growth hormone, prolactin and TSH β -subunit, and controlling development of the anterior pituitary cells in which these hormones are produced. POU1F1 is a conserved protein comprising three main domains, an N-terminal transcription activation domain (TAD), a POU-specific domain and a C-terminal homeodomain. Within the TAD, a β -domain can be inserted by alternative splicing, giving an extended ' β -variant' with altered properties...
January 11, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29334379/highly-parallel-direct-rna-sequencing-on-an-array-of-nanopores
#17
Daniel R Garalde, Elizabeth A Snell, Daniel Jachimowicz, Botond Sipos, Joseph H Lloyd, Mark Bruce, Nadia Pantic, Tigist Admassu, Phillip James, Anthony Warland, Michael Jordan, Jonah Ciccone, Sabrina Serra, Jemma Keenan, Samuel Martin, Luke McNeill, E Jayne Wallace, Lakmal Jayasinghe, Chris Wright, Javier Blasco, Stephen Young, Denise Brocklebank, Sissel Juul, James Clarke, Andrew J Heron, Daniel J Turner
Sequencing the RNA in a biological sample can unlock a wealth of information, including the identity of bacteria and viruses, the nuances of alternative splicing or the transcriptional state of organisms. However, current methods have limitations due to short read lengths and reverse transcription or amplification biases. Here we demonstrate nanopore direct RNA-seq, a highly parallel, real-time, single-molecule method that circumvents reverse transcription or amplification steps. This method yields full-length, strand-specific RNA sequences and enables the direct detection of nucleotide analogs in RNA...
January 15, 2018: Nature Methods
https://www.readbyqxmd.com/read/29331391/microrna-mediated-regulation-of-splicing-factors-srsf1-srsf2-and-hnrnp-a1-in-context-of-their-alternatively-spliced-3-utrs
#18
Elżbieta Sokół, Hanna Kędzierska, Alicja Czubaty, Beata Rybicka, Katarzyna Rodzik, Zbigniew Tański, Joanna Bogusławska, Agnieszka Piekiełko-Witkowska
SRSF1, SRSF2 and hnRNP A1 are splicing factors that regulate the expression of oncogenes and tumor suppressors. SRSF1 and SRSF2 contribute to the carcinogenesis in the kidney. Despite their importance, the mechanisms regulating their expression in cancer are not entirely understood. Here, we investigated the microRNA-mediated regulation of SRSF1, SRSF2 and hnRNP A1 in renal cancer. The expression of microRNAs predicted to target SRSF1, SRSF2 and hnRNP A1 was disturbed in renal tumors compared with controls...
January 10, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29331264/altered-levels-of-the-splicing-factor-muscleblind-modifies-cerebral-cortical-function-in-mouse-models-of-myotonic-dystrophy
#19
Gang Chen, Russell E Carter, John D Cleary, Tammy S Reid, Laura P Ranum, Maurice S Swanson, Timothy J Ebner
Myotonic dystrophy (DM) is a progressive, multisystem disorder affecting skeletal muscle, heart, and central nervous system. In both DM1 and DM2, microsatellite expansions of CUG and CCUG RNA repeats, respectively, accumulate and disrupt functions of alternative splicing factors, including muscleblind (MBNL) proteins. Grey matter loss and white matter changes, including the corpus callosum, likely underlie cognitive and executive function deficits in DM patients. However, little is known how cerebral cortical circuitry changes in DM...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29330351/the-vegfa165b-isoform-is-dysregulated-in-senescent-endothelial-cells-and-may-be-associated-with-prevalent-and-incident-coronary-heart-disease
#20
Eva Latorre, Luke C Pilling, Benjamin P Lee, Stefania Bandinelli, David Melzer, Luigi Ferrucci, Lorna W Harries
Coronary heart disease (CHD) is a leading cause of morbidity in the over 65s; over 40% of all deaths are due to this condition. The association between increasing age and CHD is well-documented; the accumulation of senescent cells in cardiac and vascular tissues may represent one factor underpinning this observation. We aimed to identify senescence-related expression changes in primary human senescent cardiomyocytes and endothelial cells and to relate transcript expression in peripheral blood leucocytes to prevalent and incident CHD in the InCHIANTI study of aging...
January 12, 2018: Clinical Science (1979-)
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