keyword
https://read.qxmd.com/read/32818388/-lmna-missense-mutation-causes-nonsense-mediated-mrna-decay-and-severe-dilated-cardiomyopathy
#21
JOURNAL ARTICLE
Koichi Kato, Seiko Ohno, Keiko Sonoda, Megumi Fukuyama, Takeru Makiyama, Tomoya Ozawa, Minoru Horie
BACKGROUND: LMNA is a known causative gene of dilated cardiomyopathy and familial conduction disturbance. Nonsense-mediated mRNA decay, normally caused by nonsense mutations, is a safeguard process to protect cells from deleterious effects of inappropriate proteins from mutated genes. Nonsense-mediated mRNA decay induced by nonstop codon mutations is rare. We investigated the effect of an LMNA missense mutation identified in 2 families affected by cardiac laminopathy. METHODS: Genomic DNA and total RNA were isolated from patients' peripheral blood lymphocytes or cardiac tissue...
October 2020: Circulation. Genomic and Precision Medicine
https://read.qxmd.com/read/32813261/epitranscriptomics-in-the-heart-a-focus-on-m-6-a
#22
REVIEW
Jacob Z Longenecker, Christopher J Gilbert, Volha A Golubeva, Colton R Martens, Federica Accornero
PURPOSE OF REVIEW: Post-transcriptional modifications are key regulators of gene expression that allow the cell to respond to environmental stimuli. The most abundant internal mRNA modification is N6-methyladenosine (m6 A), which has been shown to be involved in the regulation of RNA splicing, localization, translation, and decay. It has also been implicated in a wide range of diseases, and here, we review recent evidence of m6 A's involvement in cardiac pathologies and processes. RECENT FINDINGS: Studies have primarily relied on gain and loss of function models for the enzymes responsible for adding and removing the m6 A modification...
August 19, 2020: Current Heart Failure Reports
https://read.qxmd.com/read/32764610/rna-polymerase-ii-subunit-d-is-essential-for-zebrafish-development
#23
JOURNAL ARTICLE
Masanari Maeta, Miku Kataoka, Yusuke Nishiya, Kazutoyo Ogino, Makoto Kashima, Hiromi Hirata
DNA-directed RNA polymerase II (pol II) is composed of ten core and two dissociable subunits. The dissociable subcomplex is a heterodimer of Rpb4/Polr2d and Rpb7/Polr2g, which are encoded by RPB4/polr2d and RPB7/polr2g genes, respectively. Functional studies of Rpb4/Polr2d in yeast have revealed that Rpb4 plays a role primarily in pol II-mediated RNA synthesis and partly in various mRNA regulations including pre-mRNA splicing, nuclear export of mRNAs and decay of mRNAs. Although Rpb4 is evolutionally highly conserved from yeast to human, it is dispensable for survival in budding yeast S...
August 6, 2020: Scientific Reports
https://read.qxmd.com/read/32437714/pum2-mediates-sirt1-mrna-decay-and-exacerbates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis
#24
JOURNAL ARTICLE
Yuanping Cao, Caiyun Liu, Qun Wang, Wenjun Wang, Ende Tao, Li Wan
Pum2 is a ribonucleic acid binding protein that controls target mRNA turnover. It has been reported to be potentially associated with cardiac fibrosis. However, little is known about the role of Pum2 in cardiac disease. In this study, we found that Pum2 was upregulated in the rat heart tissue subjected to ischemia/reperfusion procedure and cultured neonatal rat ventricular cardiomyocytes (NRVMs) with hypoxia/reoxygenation (H/R) treatment. Further, knockdown of Pum2 showed a beneficial effect on H/R treated NRVMs through decreasing caspase 3-associated apoptosis, whereas overexpression of Pum2 increased H/R-induced NRVMs apoptosis...
August 1, 2020: Experimental Cell Research
https://read.qxmd.com/read/32226389/combinatorial-treatment-of-human-cardiac-engineered-tissues-with-biomimetic-cues-induces-functional-maturation-as-revealed-by-optical-mapping-of-action-potentials-and-calcium-transients
#25
JOURNAL ARTICLE
Andy On-Tik Wong, Nicodemus Wong, Lin Geng, Maggie Zi-Ying Chow, Eugene K Lee, Hongkai Wu, Michelle Khine, Chi-Wing Kong, Kevin D Costa, Wendy Keung, Yiu-Fai Cheung, Ronald A Li
Although biomimetic stimuli, such as microgroove-induced alignment (μ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+ )-handling, and molecular analyses...
2020: Frontiers in Physiology
https://read.qxmd.com/read/31878108/specific-upregulation-of-trpc1-and-trpc5-channels-by-mineralocorticoid-pathway-in-adult-rat-ventricular-cardiomyocytes
#26
JOURNAL ARTICLE
Fiona Bartoli, Soraya Moradi Bachiller, Fabrice Antigny, Kaveen Bedouet, Pascale Gerbaud, Jessica Sabourin, Jean-Pierre Benitah
Whereas cardiac TRPC (transient receptor potential canonical) channels and the associated store-operated Ca2+ entry (SOCE) are abnormally elevated during cardiac hypertrophy and heart failure, the mechanism of this upregulation is not fully elucidated but might be related to the activation of the mineralocorticoid pathway. Using a combination of biochemical, Ca2+ imaging, and electrophysiological techniques, we determined the effect of 24-h aldosterone treatment on the TRPCs/Orai-dependent SOCE in adult rat ventricular cardiomyocytes (ARVMs)...
December 23, 2019: Cells
https://read.qxmd.com/read/31756302/peripheral-blood-rna-levels-of-qsox1-and-plbd1-are-new-independent-predictors-of-left-ventricular-dysfunction-after-acute-myocardial-infarction
#27
JOURNAL ARTICLE
Maarten Vanhaverbeke, Mélanie Vausort, Denise Veltman, Lu Zhang, Ming Wu, Griet Laenen, Hilde Gillijns, Yves Moreau, Jozef Bartunek, Frans Van De Werf, Yvan Devaux, Stefan Janssens, Peter R Sinnaeve
Background - The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction. Methods - We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole blood RNA profiling at different time points...
November 22, 2019: Circulation. Genomic and Precision Medicine
https://read.qxmd.com/read/31024060/recessive-des-cardio-myopathy-without-myofibrillar-aggregates-intronic-splice-variant-silences-one-allele-leaving-only-missense-l190p-desmin
#28
JOURNAL ARTICLE
Lisa G Riley, Leigh B Waddell, Roula Ghaoui, Frances J Evesson, Beryl B Cummings, Samantha J Bryen, Himanshu Joshi, Min-Xia Wang, Susan Brammah, Leonard Kritharides, Alastair Corbett, Daniel G MacArthur, Sandra T Cooper
We establish autosomal recessive DES variants p.(Leu190Pro) and a deep intronic splice variant causing inclusion of a frameshift-inducing artificial exon/intronic fragment, as the likely cause of myopathy with cardiac involvement in female siblings. Both sisters presented in their twenties with slowly progressive limb girdle weakness, severe systolic dysfunction, and progressive, severe respiratory weakness. Desmin is an intermediate filament protein typically associated with autosomal dominant myofibrillar myopathy with cardiac involvement...
August 2019: European Journal of Human Genetics: EJHG
https://read.qxmd.com/read/30189253/tarp-syndrome-long-term-survival-anatomic-patterns-of-congenital-heart-defects-differential-diagnosis-and-pathogenetic-considerations
#29
REVIEW
Marcello Niceta, Sabina Barresi, Francesca Pantaleoni, Rossella Capolino, Maria Lisa Dentici, Andrea Ciolfi, Simone Pizzi, Andrea Bartuli, Bruno Dallapiccola, Marco Tartaglia, Maria Cristina Digilio
TARP syndrome (TARPS) is an X-linked syndromic condition including Robin sequence, congenital heart defects, developmental delay, feeding difficulties and talipes equinovarus, as major features. The disease is caused by inactivating mutations in RBM10 which encodes for a RNA binding motif protein involved in transcript processing. We herein report a male born from healthy and non-consanguineous parents, presenting prenatal record of intrauterine fetal growth retardation, and postnatal features including growth and developmental delays, CNS abnormalities, facial dysmorphisms, bilateral syndactyly at the hands, talipes equinovarus and congenital heart defects...
June 2019: European Journal of Medical Genetics
https://read.qxmd.com/read/30025651/snx17-produces-anti-arrhythmic-effects-by-preserving-functional-serca2a-protein-in-myocardial-infarction
#30
JOURNAL ARTICLE
Dandan Zhao, Xuelian Li, Haihai Liang, Nan Zheng, Zhenwei Pan, Yuhong Zhou, Xiao Liu, Ming Qian, Bozhi Xu, Ying Zhang, Ying Feng, Muge Qili, Qiuxia Wu, Baofeng Yang, Hongli Shan
BACKGROUND: Sorting nexin 17 (SNX17) is a critical cytoplasmic adaptor protein that regulates endosomal trafficking of membrane proteins to determine their recycling and/or degradation. The potential role of SNX17 in cardiovascular pathophysiology has not been reported. METHODS AND RESULTS: Cardiac arrhythmias were monitored using standard limb lead II electrocardiograph, and cardiac performances were determined by echocardiography in a rat model of myocardial infarction (MI) created by left anterior descending coronary artery ligation...
December 1, 2018: International Journal of Cardiology
https://read.qxmd.com/read/29656860/truncating-variants-in-naa15-are-associated-with-variable-levels-of-intellectual-disability-autism-spectrum-disorder-and-congenital-anomalies
#31
JOURNAL ARTICLE
Hanyin Cheng, Avinash V Dharmadhikari, Sylvia Varland, Ning Ma, Deepti Domingo, Robert Kleyner, Alan F Rope, Margaret Yoon, Asbjørg Stray-Pedersen, Jennifer E Posey, Sarah R Crews, Mohammad K Eldomery, Zeynep Coban Akdemir, Andrea M Lewis, Vernon R Sutton, Jill A Rosenfeld, Erin Conboy, Katherine Agre, Fan Xia, Magdalena Walkiewicz, Mauro Longoni, Frances A High, Marjon A van Slegtenhorst, Grazia M S Mancini, Candice R Finnila, Arie van Haeringen, Nicolette den Hollander, Claudia Ruivenkamp, Sakkubai Naidu, Sonal Mahida, Elizabeth E Palmer, Lucinda Murray, Derek Lim, Parul Jayakar, Michael J Parker, Stefania Giusto, Emanuela Stracuzzi, Corrado Romano, Jennifer S Beighley, Raphael A Bernier, Sébastien Küry, Mathilde Nizon, Mark A Corbett, Marie Shaw, Alison Gardner, Christopher Barnett, Ruth Armstrong, Karin S Kassahn, Anke Van Dijck, Geert Vandeweyer, Tjitske Kleefstra, Jolanda Schieving, Marjolijn J Jongmans, Bert B A de Vries, Rolph Pfundt, Bronwyn Kerr, Samantha K Rojas, Kym M Boycott, Richard Person, Rebecca Willaert, Evan E Eichler, R Frank Kooy, Yaping Yang, Joseph C Wu, James R Lupski, Thomas Arnesen, Gregory M Cooper, Wendy K Chung, Jozef Gecz, Holly A F Stessman, Linyan Meng, Gholson J Lyon
N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15...
May 3, 2018: American Journal of Human Genetics
https://read.qxmd.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
#32
JOURNAL ARTICLE
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...
June 2, 2017: Nucleic Acids Research
https://read.qxmd.com/read/26489465/post-transcriptional-regulation-of-nkx2-5-by-rhau-in-heart-development
#33
JOURNAL ARTICLE
Junwei Nie, Mingyang Jiang, Xiaotian Zhang, Hao Tang, Hengwei Jin, Xinyi Huang, Baiyin Yuan, Chenxi Zhang, Janice Ching Lai, Yoshikuni Nagamine, Dejing Pan, Wengong Wang, Zhongzhou Yang
RNA G-quadruplexes (G4s) play important roles in RNA biology. However, the function and regulation of mRNA G-quadruplexes in embryonic development remain elusive. Previously, we identified RHAU (DHX36, G4R1) as an RNA helicase that resolves mRNA G-quadruplexes. Here, we find that cardiac deletion of Rhau leads to heart defects and embryonic lethality in mice. Gene expression profiling identified Nkx2-5 mRNA as a target of RHAU that associates with its 5' and 3' UTRs and modulates its stability and translation...
October 27, 2015: Cell Reports
https://read.qxmd.com/read/25772296/contribution-of-sodium-channel-neuronal-isoform-nav1-1-to-late-sodium-current-in-ventricular-myocytes-from-failing-hearts
#34
JOURNAL ARTICLE
Sudhish Mishra, Vitaliy Reznikov, Victor A Maltsev, Nidas A Undrovinas, Hani N Sabbah, Albertas Undrovinas
KEY POINTS: Late Na(+) current (INaL) contributes to action potential remodelling and Ca(2+)/Na(+) changes in heart failure. The molecular identity of INaL remains unclear. The contributions of different Na(+) channel isoforms, apart from the cardiac isoform, remain unknown. We discovered and characterized a substantial contribution of neuronal isoform Nav1.1 to INaL. This new component is physiologically relevant to the control of action potential shape and duration, as well as to cell Ca(2+) dynamics, especially in heart failure...
March 15, 2015: Journal of Physiology
https://read.qxmd.com/read/25326451/contribution-of-neuronal-isoform-nav1-1-to-late-sodium-current-in-ventricular-myocytes-from-failing-hearts
#35
Sudhish Mishra, Vitaliy Reznikov, Victor A Maltsev, Nidas A Undrovinas, Hani N Sabbah, Albertas Undrovinas
Late Na(+) current (INaL) contributes to action potential (AP) duration and Ca(2+) handling in cardiac cells. Augmented INaL was implicated in delayed repolarization and impaired Ca(2+) handling in heart failure (HF). We tested if Na(+) channel (Nav's) neuronal isoforms contribute to INaL and Ca(2+) cycling defects in HF in 17 dogs with HF achieved via sequential coronary artery embolizations. Six normal dogs served as control. Transient Na(+) current (INaT) and INaL in left ventricular cardiomyocytes (VCMs) were recorded by patch-clamp while Ca(2+) dynamics was monitored using fluo-4...
October 17, 2014: Journal of Physiology
https://read.qxmd.com/read/25252951/progesterone-modulates-serca2a-expression-and-function-in-rabbit-cardiomyocytes
#36
JOURNAL ARTICLE
Karni S Moshal, Zhe Zhang, Karim Roder, Tae Yun Kim, Leroy Cooper, Bogdan Patedakis Litvinov, Yichun Lu, Vishal Reddy, Dmitry Terentyev, Bum-Rak Choi, Gideon Koren
We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo)plasmic reticulum Ca(2+)-ATPase type 2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca(2+)-dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes...
December 1, 2014: American Journal of Physiology. Cell Physiology
https://read.qxmd.com/read/25064126/intracellular-calcium-regulates-nonsense-mediated-mrna-decay
#37
JOURNAL ARTICLE
Andrew Nickless, Erin Jackson, Jayne Marasa, Patrick Nugent, Robert W Mercer, David Piwnica-Worms, Zhongsheng You
The nonsense-mediated mRNA decay (NMD) pathway selectively eliminates aberrant transcripts containing premature translation termination codons and regulates the levels of a number of physiological mRNAs. NMD modulates the clinical outcome of a variety of human diseases, including cancer and many genetic disorders, and may represent a target for therapeutic intervention. Here, we have developed a new multicolored bioluminescence-based reporter system that can specifically and effectively assay NMD in live human cells...
August 2014: Nature Medicine
https://read.qxmd.com/read/24361238/p38%C3%AE-regulates-serca2a-function
#38
JOURNAL ARTICLE
Leena Kaikkonen, Johanna Magga, Veli-Pekka Ronkainen, Elina Koivisto, Ábel Perjes, J Kurt Chuprun, Leif Erik Vinge, Teemu Kilpiö, Jani Aro, Johanna Ulvila, Tarja Alakoski, James A Bibb, Istvan Szokodi, Walter J Koch, Heikki Ruskoaho, Risto Kerkelä
cAMP-dependent protein kinase (PKA) regulates the L-type calcium channel, the ryanodine receptor, and phospholamban (PLB) thereby increasing inotropy. Cardiac contractility is also regulated by p38 MAPK, which is a negative regulator of cardiac contractile function. The aim of this study was to identify the mechanism mediating the positive inotropic effect of p38 inhibition. Isolated adult and neonatal cardiomyocytes and perfused rat hearts were utilized to investigate the molecular mechanisms regulated by p38...
February 2014: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/24321233/nonsense-mediated-mrna-decay-due-to-a-cacna1c-splicing-mutation-in-a-patient-with-brugada-syndrome
#39
JOURNAL ARTICLE
Megumi Fukuyama, Seiko Ohno, Qi Wang, Takeshi Shirayama, Hideki Itoh, Minoru Horie
BACKGROUND: Brugada syndrome (BrS) is an inherited cardiac arrhythmia associated with sudden death due to ventricular fibrillation. Mutations in genes related to the cardiac L-type calcium channel have been reported to be causative of BrS. Generally, the messenger RNA (mRNA) that contains a nonsense mutation is rapidly degraded via its decay pathway, which is known as nonsense-mediated mRNA decay (NMD). Previously, we reported a male patient with BrS who carried c.1896G>A (the first nucleotide of CACNA1C exon 14), which caused a synonymous mutation, p...
April 2014: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://read.qxmd.com/read/24098136/a-novel-actin-mrna-splice-variant-regulates-actg1-expression
#40
JOURNAL ARTICLE
Meghan C Drummond, Karen H Friderici
Cytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However, actin expression is regulated in a tissue- and development-specific manner. We identified a novel cytoplasmic-γ-actin (Actg1) transcript that includes a previously unidentified exon (3a). Inclusion of this exon introduces an in-frame termination codon. We hypothesized this alternatively-spliced transcript down-regulates γ-actin production by targeting these transcripts for nonsense-mediated decay (NMD). To address this, we investigated conservation between mammals, tissue-specificity in mice, and developmental regulation using C2C12 cell culture...
2013: PLoS Genetics
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