15,087 results match your criteria intron splicing

Mouse totipotent stem cells captured and maintained through spliceosomal repression.

Cell 2021 May 10. Epub 2021 May 10.

MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address:

Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Read More

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Parallel and Population-specific Gene Regulatory Evolution in Cold-Adapted Fly Populations.

Genetics 2021 May 14. Epub 2021 May 14.

Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. Read More

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LAMB2 novel variant c.2885-9 C>A affects RNA splicing in a minigene assay.

Mol Genet Genomic Med 2021 May 13:e1704. Epub 2021 May 13.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants. Read More

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Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection.

Cell 2021 May 4. Epub 2021 May 4.

Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address:

The activities of RNA polymerase and the spliceosome are responsible for the heterogeneity in the abundance and isoform composition of mRNA in human cells. However, the dynamics of these megadalton enzymatic complexes working in concert on endogenous genes have not been described. Here, we establish a quasi-genome-scale platform for observing synthesis and processing kinetics of single nascent RNA molecules in real time. Read More

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A termination-independent role of Rat1 in cotranscriptional splicing.

Nucleic Acids Res 2021 May 12. Epub 2021 May 12.

Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.

Rat1 is a 5'→3' exoribonuclease in budding yeast. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its human homolog Xrn2 have been implicated in multiple nuclear processes. Read More

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The RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium.

Nat Commun 2021 May 11;12(1):2661. Epub 2021 May 11.

State Key Laboratory of Rice Biology, the Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Precursor messenger RNA (pre-mRNA) splicing is an essential and tightly regulated process in eukaryotic cells; however, the regulatory mechanisms for the splicing are not well understood. Here, we characterize a RNA binding protein named FgRbp1 in Fusarium graminearum, a fungal pathogen of cereal crops worldwide. Deletion of FgRbp1 leads to reduced splicing efficiency in 47% of the F. Read More

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Co-transcriptional splicing efficiencies differ within genes and between cell types.

RNA 2021 May 11. Epub 2021 May 11.

University of Michigan

Pre-mRNA splicing is carried out by the spliceosome and involves splice site recognition, removal of introns, and ligation of exons. Components of the spliceosome have been shown to interact with the elongating RNA polymerase II (RNAPII) which is thought to allow splicing to occur concurrently with transcription. However, little is known about the regulation and efficiency of co-transcriptional splicing in human cells. Read More

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Vps34 and TOR Kinases Coordinate mRNA Translation in the presence or absence of Ire1-dependent Splicing.

Mol Cell Biol 2021 May 10. Epub 2021 May 10.

Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI-53211, USA

In the budding yeast an mRNA, called , exists in a translationally repressed form in the cytoplasm. Under conditions of cellular stress, such as when unfolded proteins accumulate inside the endoplasmic reticulum (ER), an RNase Ire1 removes an intervening sequence (intron) from the mRNA by non-conventional cytosolic splicing. Removal of the intron results in translational de-repression of mRNA and production of a transcription factor that activates expressions of many enzymes and chaperones to increase the protein-folding capacity of the cell. Read More

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Mutations in cis that affect mRNA synthesis, processing and translation.

Biochim Biophys Acta Mol Basis Dis 2021 May 7:166166. Epub 2021 May 7.

Sanquin Blood Supply Organization, Dept. of Blood Cell Research, and Landsteiner Laboratory, Amsterdam University Medical Centre, location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Genetic mutations that cause hereditary diseases usually affect the composition of the transcribed mRNA and its encoded protein, leading to instability of the mRNA and/or the protein. Sometimes, however, such mutations affect the synthesis, the processing or the translation of the mRNA, with similar disastrous effects. We here present an overview of mRNA synthesis, its posttranscriptional modification and its translation into protein. Read More

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Gene Architecture Facilitates Intron-Mediated Enhancement of Transcription.

Front Mol Biosci 2021 21;8:669004. Epub 2021 Apr 21.

Department of Biological Science, Wayne State University, Detroit, MI, United States.

Introns impact several vital aspects of eukaryotic organisms like proteomic plasticity, genomic stability, stress response and gene expression. A role for introns in the regulation of gene expression at the level of transcription has been known for more than thirty years. The molecular basis underlying the phenomenon, however, is still not entirely clear. Read More

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-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems.

Open Med (Wars) 2021 12;16(1):640-650. Epub 2021 Apr 12.

Sahlgrenska University Hospital, Gothia Forum for Clinical Research, Gothenburg, Sweden.

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. Read More

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Overlapping roles of spliceosomal components SF3B1 and PHF5A in rice splicing regulation.

Commun Biol 2021 May 5;4(1):529. Epub 2021 May 5.

Laboratory for Genome Engineering and Synthetic Biology, King Abdullah, University of Science and Technology (KAUST), Thuwal, Saudi Arabia.

The SF3B complex, a multiprotein component of the U2 snRNP of the spliceosome, plays a crucial role in recognizing branch point sequence and facilitates spliceosome assembly and activation. Several chemicals that bind SF3B1 and PHF5A subunits of the SF3B complex inhibit splicing. We recently generated a splicing inhibitor-resistant SF3B1 mutant named SF3B1 GEX1A RESISTANT 4 (SGR4) using CRISPR-mediated directed evolution, whereas splicing inhibitor-resistant mutant of PHF5A (Overexpression-PHF5A GEX1A Resistance, OGR) was generated by expressing an engineered version PHF5A-Y36C. Read More

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SAM homeostasis is regulated by CFI-mediated splicing of MAT2A.

Elife 2021 May 5;10. Epub 2021 May 5.

Microbiology, University of Texas Southwestern Medical Center, Dallas, United States.

S-adenosylmethionine (SAM) is the methyl donor for nearly all cellular methylation events. Cells regulate intracellular SAM levels through intron detention of MAT2A, the only SAM synthetase expressed in most cells. The N-adenosine methyltransferase METTL16 promotes splicing of the MAT2A detained intron by an unknown mechanism. Read More

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A novel essential splice site variant in SPTB in a large hereditary spherocytosis family.

Mol Genet Genomic Med 2021 May 4:e1641. Epub 2021 May 4.

Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA.

Background: We studied a large family with 22 individuals affected with autosomal dominant hereditary spherocytosis (HS).

Methods: Genome-wide linkage, whole-genome sequencing (WGS), Sanger sequencing, RT-PCR, and ToPO TA cloning analyses were performed.

Results: We revealed a heterozygous G>A transition in the 14q23 locus, at position +1 of the intron 8 donor splice site of the spectrin beta, erythrocytic (SPTB) gene. Read More

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A drug-repositioning screen using splicing-sensitive fluorescent reporters identifies novel modulators of VEGF-A splicing with anti-angiogenic properties.

Oncogenesis 2021 May 3;10(5):36. Epub 2021 May 3.

Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke's Campus, Exeter, EX1 2LU, UK.

Alternative splicing of the vascular endothelial growth factor A (VEGF-A) terminal exon generates two protein families with differing functions. Pro-angiogenic VEGF-Aa isoforms are produced via selection of the proximal 3' splice site of the terminal exon. Use of an alternative distal splice site generates the anti-angiogenic VEGF-Ab proteins. Read More

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Meta-Analyses of Splicing and Expression Quantitative Trait Loci Identified Susceptibility Genes of Glioma.

Front Genet 2021 15;12:609657. Epub 2021 Apr 15.

Department of Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA, United States.

Background: The functions of most glioma risk alleles are unknown. Very few studies had evaluated expression quantitative trait loci (eQTL), and insights of susceptibility genes were limited due to scarcity of available brain tissues. Moreover, no prior study had examined the effect of glioma risk alleles on alternative RNA splicing. Read More

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A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer's disease.

Acta Neuropathol 2021 May 2. Epub 2021 May 2.

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM). Nicolás Cabrera, 1. Cantoblanco, 28049, Madrid, Spain.

Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with Tau pathology (FTLD-tau), are a group of neurodegenerative disorders characterized by Tau hyperphosphorylation. Post-translational modifications of Tau such as phosphorylation and truncation have been demonstrated to be an essential step in the molecular pathogenesis of these tauopathies. In this work, we demonstrate the existence of a new, human-specific truncated form of Tau generated by intron 12 retention in human neuroblastoma cells and, to a higher extent, in human RNA brain samples, using qPCR and further confirming the results on a larger database of human RNA-seq samples. Read More

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Splice Variants of Superoxide Dismutases in Rice and Their Expression Profiles under Abiotic Stresses.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.

The superoxide dismutases (SODs) play vital roles in controlling cellular reactive oxygen species (ROS) that are generated both under optimal as well as stress conditions in plants. The rice genome harbors seven SOD genes (, , , , , and ) that encode seven constitutive transcripts. Of these, five (, , , and ) utilizes an alternative splicing (AS) strategy and generate seven additional splice variants () or mRNA variants, i. Read More

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Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer.

Cells 2021 Apr 16;10(4). Epub 2021 Apr 16.

Division of Gene Therapy Science, Department of Genome Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Read More

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Translational Attenuation by an Intron Retention in the 5' UTR of Causes Amelogenesis Imperfecta.

Biomedicines 2021 Apr 22;9(5). Epub 2021 Apr 22.

Department of Molecular Genetics & DRI, School of Dentistry, Seoul National University, Seoul 03080, Korea.

Amelogenesis imperfecta (AI) is a collection of rare genetic conditions affecting tooth enamel. The affected enamel can be of insufficient quantity and/or altered quality, impacting structural content, surface integrity and coloration. Heterozygous mutations in result in hypoplastic AI without other syndromic phenotypes, with variable expressivity and reduced penetrance, unlike other AI-associated genes. Read More

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MET Exon 14 Skipping: A Case Study for the Detection of Genetic Variants in Cancer Driver Genes by Deep Learning.

Int J Mol Sci 2021 Apr 19;22(8). Epub 2021 Apr 19.

Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.

Background: Disruption of alternative splicing (AS) is frequently observed in cancer and might represent an important signature for tumor progression and therapy. Exon skipping (ES) represents one of the most frequent AS events, and in non-small cell lung cancer (NSCLC) MET exon 14 skipping was shown to be targetable.

Methods: We constructed neural networks (NN/CNN) specifically designed to detect MET exon 14 skipping events using RNAseq data. Read More

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Novel manifestations of Warburg micro syndrome type 1 caused by a new splicing variant of RAB3GAP1: a case report.

BMC Neurol 2021 Apr 28;21(1):180. Epub 2021 Apr 28.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: The present study aimed to determine the underlying genetic factors causing the possible Warburg micro syndrome (WARBM) phenotype in two Iranian patients.

Case Presentation: A 5-year-old female and a 4.5-year-old male were referred due to microcephaly, global developmental delay, and dysmorphic features. Read More

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Identification of a novel mutation in congenital afibrinogenemia in Iranian patients.

Blood Coagul Fibrinolysis 2021 Apr 23. Epub 2021 Apr 23.

Kawsar Human Genetics Research Center, Tehran Dr Davarnia Genetic Counseling and Diagnosis Center, Imam Reza Hospital, Ardabil Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS) Department of Medical Genetics, Ali-Asghar Children's Hospital Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Congenital afibrinogenemia is a rare autosomal recessive disorder that is caused by defects in the fibrinogen. Fibrinogen is a hexameric glycoprotein made of two pairs of three homologous polypeptide chains including Aα, Bβ, and γ that are encoded by three genes named FGA, FGB, and FGG. We aim to study four Iranian families who were referred to our lab for molecular diagnosis of afibrinogenemia. Read More

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Cotranscriptional and Posttranscriptional Features of the Transcriptome in Soybean Shoot Apex and Leaf.

Front Plant Sci 2021 9;12:649634. Epub 2021 Apr 9.

Guangzhou Key Laboratory of Crop Gene Editing, Innovative Center of Molecular Genetics and Evolution, School of Life Sciences, Guangzhou Higher Education Mega Center, Guangzhou University, Guangzhou, China.

Transcription is the first step of central dogma, in which the genetic information stored in DNA is copied into RNA. In addition to mature RNA sequencing (RNA-seq), high-throughput nascent RNA assays have been established and applied to provide detailed transcriptional information. Here, we present the profiling of nascent RNA from trifoliate leaves and shoot apices of soybean. Read More

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Minor Intron Splicing Regulates Hematopoietic Stem Cell Self-Renewal.


Cancer Discov 2021 Apr 23. Epub 2021 Apr 23.

Loss of ZRSR2, frequently mutated in blood cancer, enhanced hematopoietic stem cell self-renewal. Read More

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Exploring the Alternative Splicing of Long Noncoding RNAs.

Trends Genet 2021 Apr 20. Epub 2021 Apr 20.

Research Center on Aging, Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada; Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:

Like protein-coding genes, long noncoding RNA (lncRNA) genes are composed of introns and exons. After their transcription, lncRNAs are subject to constitutive and/or alternative splicing. Here, we describe the current knowledge on lncRNA splice variants and their functional implications in cell biology. Read More

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Identification of polycistronic transcriptional units and non-canonical introns in green algal chloroplasts based on long-read RNA sequencing data.

BMC Genomics 2021 Apr 23;22(1):298. Epub 2021 Apr 23.

Environment and Plant Protection Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, Hainan, P. R. China.

Background: Chloroplasts are important semi-autonomous organelles in plants and algae. Unlike higher plants, the chloroplast genomes of green algal linage have distinct features both in organization and expression. Despite the architecture of chloroplast genome having been extensively studied in higher plants and several model species of algae, little is known about the transcriptional features of green algal chloroplast-encoded genes. Read More

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A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist.

PLoS Biol 2021 Apr 23;19(4):e3001126. Epub 2021 Apr 23.

Department of Zoology, University of Oxford, Oxford, United Kingdom.

The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss. Therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. Read More

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Variants in STXBP3 Are Associated With Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.

J Crohns Colitis 2021 Apr 23. Epub 2021 Apr 23.

Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA.

Background And Aims: Very early onset inflammatory bowel disease (VEOIBD) is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic etiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. Read More

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The PPR-SMR Protein ATP4 Is Required for Editing the Chloroplast rps8 mRNA in Rice and Maize.

Plant Physiol 2020 Dec;184(4):2011-2021

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

Chloroplast gene expression involves the participation of hundreds of pentatricopeptide repeat (PPR) RNA binding proteins, and proteins in the PLS subfamily typically specify sites of RNA editing, whereas those in the P-subfamily typically stabilize RNA, activate translation, or promote intron splicing. Several P-type PPR proteins include a small MutS-related (SMR) domain, but the biochemical contribution of the SMR domain remains enigmatic. Here, we describe a rice (Oryza sativa) mutant, osatp4, lacking the ortholog of ATP4, a PPR-SMR protein in maize (Zea mays). Read More

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December 2020