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  • 1
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    Exosome-mediated recognition and degradation of mRNAs lacking a termination codon (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-03-23
    Description: One role of messenger RNA (mRNA) degradation is to maintain the fidelity of gene expression by degrading aberrant transcripts. Recent results show that mRNAs without translation termination codons are unstable in eukaryotic cells. We used yeast mutants to demonstrate that these "nonstop" mRNAs are degraded by the exosome in a 3'-to-5' direction. The degradation of nonstop transcripts requires the exosome-associated protein Ski7p. Ski7p is closely related to the translation elongation factor EF1A and the translation termination factor eRF3. This suggests that the recognition of nonstop mRNAs involves the binding of Ski7p to an empty aminoacyl-(RNA-binding) site (A site) on the ribosome, thereby bringing the exosome to a mRNA with a ribosome stalled near the 3' end. This system efficiently degrades mRNAs that are prematurely polyadenylated within the coding region and prevents their expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Hoof, Ambro -- Frischmeyer, Pamela A -- Dietz, Harry C -- Parker, Roy -- New York, N.Y. -- Science. 2002 Mar 22;295(5563):2262-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA. : ambro@u.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11910110" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Alleles ; Amino Acid Sequence ; Base Sequence ; Binding Sites ; Codon, Terminator/*genetics ; Fungal Proteins/chemistry/genetics/*metabolism ; *GTP-Binding Proteins ; Gene Expression Regulation, Fungal ; Genes, Fungal/genetics ; Half-Life ; Molecular Sequence Data ; Polyadenylation ; Protein Binding ; Protein Biosynthesis ; RNA 3' End Processing ; *RNA Processing, Post-Transcriptional ; RNA Stability ; RNA, Fungal/genetics/metabolism ; RNA, Messenger/*genetics/*metabolism ; Ribosomes/metabolism ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Sequence Alignment ; Sequence Deletion/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-09-14
    Description: The mechanism by which disruption of reading frame can influence pre-messenger RNA (pre-mRNA) processing is poorly understood. We assessed the role of factors essential for nonsense-mediated mRNA decay (NMD) in nonsense-mediated altered splicing (NAS) with the use of RNA interference (RNAi) in mammalian cells. Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T cell receptor beta transcripts. In contrast, inhibition of rent2/hUpf2 expression did not disrupt NAS despite achieving comparable stabilization of nonsense transcripts. We also demonstrate that NAS and NMD are genetically separable functions of rent1/hUpf1. Additionally, rent1/hUpf1 enters the nucleus where it may directly influence early events in mRNA biogenesis. This provides compelling evidence that NAS relies on a component of the nonsense surveillance machinery but is not an indirect consequence of NMD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendell, Joshua T -- ap Rhys, Colette M J -- Dietz, Harry C -- GM55239/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 11;298(5592):419-22. Epub 2002 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Genetic Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 858 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228722" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; *Alternative Splicing ; Amino Acid Substitution ; Blotting, Northern ; Cell Nucleus/metabolism ; *Codon, Nonsense ; Cytoplasm/metabolism ; Equilibrative-Nucleoside Transporter 2/genetics/metabolism ; Fatty Acids, Unsaturated/pharmacology ; Gene Silencing ; Genes, T-Cell Receptor beta ; HeLa Cells ; Humans ; Mutation ; RNA Helicases/genetics/*metabolism ; RNA, Messenger/genetics/*metabolism ; RNA, Small Interfering/metabolism ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/genetics/*metabolism ; Transcription Factors/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-08
    Description: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482474/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482474/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Judge, Daniel P -- Holm, Tammy M -- Cohn, Ronald D -- Loeys, Bart L -- Cooper, Timothy K -- Myers, Loretha -- Klein, Erin C -- Liu, Guosheng -- Calvi, Carla -- Podowski, Megan -- Neptune, Enid R -- Halushka, Marc K -- Bedja, Djahida -- Gabrielson, Kathleen -- Rifkin, Daniel B -- Carta, Luca -- Ramirez, Francesco -- Huso, David L -- Dietz, Harry C -- K08 HL067056/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 7;312(5770):117-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16601194" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Antagonists/administration & dosage/therapeutic use ; Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use ; Animals ; Antibodies/immunology ; Aorta/pathology ; Aortic Aneurysm/etiology/*prevention & control ; *Disease Models, Animal ; Elastic Tissue/pathology ; Female ; Losartan/administration & dosage/*therapeutic use ; Lung/pathology ; Lung Diseases/drug therapy/pathology ; Marfan Syndrome/complications/*drug therapy/metabolism/pathology ; Mice ; Microfilament Proteins/genetics ; Mutation ; Neutralization Tests ; Pregnancy ; Pregnancy Complications/drug therapy ; Propranolol/administration & dosage/therapeutic use ; Pulmonary Alveoli/pathology ; Receptor, Angiotensin, Type 1/metabolism ; Signal Transduction ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Noncanonical TGFbeta signaling contributes to aortic aneurysm progression in Marfan syndrome mice (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-04-16
    Description: Transforming growth factor-beta (TGFbeta) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFbeta can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFbeta. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFbeta signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holm, Tammy M -- Habashi, Jennifer P -- Doyle, Jefferson J -- Bedja, Djahida -- Chen, YiChun -- van Erp, Christel -- Lindsay, Mark E -- Kim, David -- Schoenhoff, Florian -- Cohn, Ronald D -- Loeys, Bart L -- Thomas, Craig J -- Patnaik, Samarjit -- Marugan, Juan J -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-12/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493862" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthracenes/pharmacology/therapeutic use ; Aorta/pathology ; Aortic Aneurysm/*metabolism/pathology/physiopathology/prevention & control ; Diphenylamine/analogs & derivatives/pharmacology/therapeutic use ; Disease Models, Animal ; Disease Progression ; Enzyme Activation ; Losartan/pharmacology/therapeutic use ; *MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Smad2 Protein/metabolism ; Smad4 Protein/deficiency/genetics ; Sulfonamides/pharmacology/therapeutic use ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-04-16
    Description: Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor-beta (TGFbeta) signaling in the aorta, but losartan uniquely inhibited TGFbeta-mediated activation of extracellular signal-regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Doyle, Jefferson J -- Holm, Tammy M -- Aziz, Hamza -- Schoenhoff, Florian -- Bedja, Djahida -- Chen, YiChun -- Modiri, Alexandra N -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):361-5. doi: 10.1126/science.1192152.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493863" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/metabolism ; Angiotensin II Type 1 Receptor Blockers/pharmacology/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic use ; Animals ; Aorta ; Aortic Aneurysm/drug therapy/*metabolism/pathology/prevention & control ; Aortic Rupture/metabolism/pathology/prevention & control ; Disease Models, Animal ; Disease Progression ; Enalapril/pharmacology/therapeutic use ; Losartan/pharmacology/therapeutic use ; MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/*antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinase 3/*antagonists & inhibitors/metabolism ; Receptor, Angiotensin, Type 2/genetics/*metabolism ; *Signal Transduction ; Transforming Growth Factor beta/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    An mRNA surveillance mechanism that eliminates transcripts lacking termination codons (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-03-23
    Description: Translation is an important mechanism to monitor the quality of messenger RNAs (mRNAs), as exemplified by the translation-dependent recognition and degradation of transcripts harboring premature termination codons (PTCs) by the nonsense-mediated mRNA decay (NMD) pathway. We demonstrate in yeast that mRNAs lacking all termination codons are as labile as nonsense transcripts. Decay of "nonstop" transcripts in yeast requires translation but is mechanistically distinguished from NMD and the major mRNA turnover pathway that requires deadenylation, decapping, and 5'-to-3' exonucleolytic decay. These data suggest that nonstop decay is initiated when the ribosome reaches the 3' terminus of the message. We demonstrate multiple physiologic sources of nonstop transcripts and conservation of their accelerated decay in mammalian cells. This process regulates the stability and expression of mRNAs that fail to signal translational termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frischmeyer, Pamela A -- van Hoof, Ambro -- O'Donnell, Kathryn -- Guerrerio, Anthony L -- Parker, Roy -- Dietz, Harry C -- GM55239/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 22;295(5563):2258-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetic Medicine, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11910109" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/chemistry/genetics/metabolism ; Base Sequence ; Cell Line ; Codon, Terminator/*genetics ; Databases, Genetic ; Genes, Fungal/genetics ; Glucuronidase/genetics ; Half-Life ; Humans ; Polyadenylation ; *Protein Biosynthesis ; RNA 3' End Processing ; *RNA Processing, Post-Transcriptional ; RNA Stability ; RNA, Messenger/chemistry/*genetics/*metabolism ; Saccharomyces cerevisiae/*genetics ; Sequence Deletion/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Lessons on the pathogenesis of aneurysm from heritable conditions (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-05-20
    Description: Aortic aneurysm is common, accounting for 1-2% of all deaths in industrialized countries. Early theories of the causes of human aneurysm mostly focused on inherited or acquired defects in components of the extracellular matrix in the aorta. Although several mutations in the genes encoding extracellular matrix proteins have been recognized, more recent discoveries have shown important perturbations in cytokine signalling cascades and intracellular components of the smooth muscle contractile apparatus. The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-beta cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622871/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindsay, Mark E -- Dietz, Harry C -- K08 HL107738/HL/NHLBI NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 19;473(7347):308-16. doi: 10.1038/nature10145.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-1832, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21593863" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/metabolism ; Animals ; Aortic Aneurysm/complications/*genetics/*pathology/therapy ; Disease Models, Animal ; Elastin/metabolism ; Humans ; Muscle, Smooth, Vascular/pathology ; Transforming Growth Factor beta/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 8
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    Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-10-11
    Description: In systemic sclerosis (SSc), a common and aetiologically mysterious form of scleroderma (defined as pathological fibrosis of the skin), previously healthy adults acquire fibrosis of the skin and viscera in association with autoantibodies. Familial recurrence is extremely rare and causal genes have not been identified. Although the onset of fibrosis in SSc typically correlates with the production of autoantibodies, whether they contribute to disease pathogenesis or simply serve as a marker of disease remains controversial and the mechanism for their induction is largely unknown. The study of SSc is hindered by a lack of animal models that recapitulate the aetiology of this complex disease. To gain a foothold in the pathogenesis of pathological skin fibrosis, we studied stiff skin syndrome (SSS), a rare but tractable Mendelian disorder leading to childhood onset of diffuse skin fibrosis with autosomal dominant inheritance and complete penetrance. We showed previously that SSS is caused by heterozygous missense mutations in the gene (FBN1) encoding fibrillin-1, the main constituent of extracellular microfibrils. SSS mutations all localize to the only domain in fibrillin-1 that harbours an Arg-Gly-Asp (RGD) motif needed to mediate cell-matrix interactions by binding to cell-surface integrins. Here we show that mouse lines harbouring analogous amino acid substitutions in fibrillin-1 recapitulate aggressive skin fibrosis that is prevented by integrin-modulating therapies and reversed by antagonism of the pro-fibrotic cytokine transforming growth factor beta (TGF-beta). Mutant mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells and plasma cells, and also autoantibody production; these findings are normalized by integrin-modulating therapies or TGF-beta antagonism. These results show that alterations in cell-matrix interactions are sufficient to initiate and sustain inflammatory and pro-fibrotic programmes and highlight new therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992987/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992987/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerber, Elizabeth E -- Gallo, Elena M -- Fontana, Stefani C -- Davis, Elaine C -- Wigley, Fredrick M -- Huso, David L -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01-AR049698/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01-AR41135/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Nov 7;503(7474):126-30. doi: 10.1038/nature12614. Epub 2013 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24107997" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Amino Acid Substitution/genetics ; Animals ; Antibodies, Antinuclear/immunology ; Antibodies, Neutralizing/immunology/pharmacology/therapeutic use ; Autoimmunity/*drug effects/immunology ; Contracture/*drug therapy/immunology/*pathology/prevention & control ; Dendritic Cells/drug effects ; Female ; Fibrosis/drug therapy/pathology/prevention & control ; Integrins/*drug effects/*metabolism ; Male ; Mice ; Microfilament Proteins/chemistry/genetics/metabolism ; Mutation, Missense/genetics ; Plasma Cells/drug effects ; Scleroderma, Systemic/*drug therapy/immunology/*pathology/prevention & control ; Skin Diseases, Genetic/*drug therapy/immunology/*pathology/prevention & control ; T-Lymphocytes, Helper-Inducer/drug effects ; Transforming Growth Factor beta/antagonists & inhibitors/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    The skipping of constitutive exons in vivo induced by nonsense mutations (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-01-29
    Description: Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dietz, H C -- Valle, D -- Francomano, C A -- Kendzior, R J Jr -- Pyeritz, R E -- Cutting, G R -- AR-41135/AR/NIAMS NIH HHS/ -- HG-00373/HG/NHGRI NIH HHS/ -- RR-00722/RR/NCRR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):680-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430317" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cells, Cultured ; DNA/*genetics/isolation & purification ; *Exons ; Female ; Fibroblasts/physiology ; Humans ; Male ; Marfan Syndrome/*genetics ; Microfilament Proteins/*genetics ; Molecular Sequence Data ; *Mutation ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction/methods ; Reference Values
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Electronic Resource
    Electronic Resource
    Molecular Genetic Approaches to the Study of Human Cardiovascular Disease (1994)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 763-796 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.56.030194.003555
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