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HnRNP A1

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https://www.readbyqxmd.com/read/29762696/blocking-of-an-intronic-splicing-silencer-completely-rescues-ikbkap-exon-20-splicing-in-familial-dysautonomia-patient-cells
#1
Gitte H Bruun, Jeanne Mv Bang, Lise L Christensen, Sabrina Brøner, Ulrika Ss Petersen, Barbara Guerra, Alexander Gb Grønning, Thomas K Doktor, Brage S Andresen
Familial dysautonomia (FD) is a severe genetic disorder causing sensory and autonomic dysfunction. It is predominantly caused by a c.2204+6T>C mutation in the IKBKAP gene. This mutation decreases the 5' splice site strength of IKBKAP exon 20 leading to exon 20 skipping and decreased amounts of full-length IKAP protein. We identified a binding site for the splicing regulatory protein hnRNP A1 downstream of the IKBKAP exon 20 5'-splice site. We show that hnRNP A1 binds to this splicing regulatory element (SRE) and that two previously described inhibitory SREs inside IKBKAP exon 20 are also bound by hnRNP A1...
May 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29625167/idiosyncrasies-of-hnrnp-a1-rna-recognition-can-binding-mode-influence-function
#2
REVIEW
Jeffrey D Levengood, Blanton S Tolbert
The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that function in most stages of RNA metabolism. The prototypical member, hnRNP A1, is composed of three major domains; tandem N-terminal RNA Recognition Motifs (RRMs) and a C-terminal mostly intrinsically disordered region. HnRNP A1 is broadly implicated in basic cellular RNA processing events such as splicing, stability, nuclear export and translation. Due to its ubiquity and abundance, hnRNP A1 is also frequently usurped to control viral gene expression...
April 3, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29562314/tdp-43-regulates-the-alternative-splicing-of-hnrnp-a1-to-yield-an-aggregation-prone-variant-in-amyotrophic-lateral-sclerosis
#3
Jade-Emmanuelle Deshaies, Lulzim Shkreta, Alexander J Moszczynski, Hadjara Sidibé, Sabrina Semmler, Aurélien Fouillen, Estelle R Bennett, Uriya Bekenstein, Laurie Destroismaisons, Johanne Toutant, Quentin Delmotte, Kathryn Volkening, Stéphanie Stabile, Anaïs Aulas, Yousra Khalfallah, Hermona Soreq, Antonio Nanci, Michael J Strong, Benoit Chabot, Christine Vande Velde
The RNA binding proteins TDP-43 (encoded by TARDBP) and hnRNP A1 (HNRNPA1) are each mutated in certain amyotrophic lateral sclerosis cases and are often mislocalized in cytoplasmic aggregates within motor neurons of affected patients. Cytoplasmic inclusions of TDP-43, which are accompanied by a depletion of nuclear TDP-43, are observed in most amyotrophic lateral sclerosis cases and nearly half of frontotemporal dementia cases. Here, we report that TDP-43 binds HNRNPA1 pre-mRNA and modulates its splicing, and that depletion of nuclear TDP-43 results in increased inclusion of a cassette exon in the HNRNPA1 transcript, and consequently elevated protein levels of an isoform containing an elongated prion-like domain, referred to as hnRNP A1B...
March 19, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29534017/cellular-hnrnp-a1-interacts-with-nucleocapsid-protein-of-porcine-epidemic-diarrhea-virus-and-impairs-viral-replication
#4
Zhonghua Li, Wei Zeng, Shiyi Ye, Jian Lv, Axiu Nie, Bingzhou Zhang, Yumei Sun, Heyou Han, Qigai He
The nucleocapsid (N) protein is a major structural component of porcine epidemic diarrhea virus (PEDV), which is predicted to be a multifunctional protein in viral replication. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a cellular protein participating in the splicing of pre-mRNA in the nucleus and translation regulation in the cytoplasm. According to our previous proteomic study about PEDV infection in vivo, hnRNP A1 was thought to be a cellular factor influencing PEDV replication. In this report, PEDV N protein was discovered to colocalize with cellular hnRNP A1 in perinuclear region of PEDV infected cells...
March 13, 2018: Viruses
https://www.readbyqxmd.com/read/29396485/hnrnp-a1-a2-and-sam68-collaborate-with-srsf10-to-control-the-alternative-splicing-response-to-oxaliplatin-mediated-dna-damage
#5
Alexandre Cloutier, Lulzim Shkreta, Johanne Toutant, Mathieu Durand, Philippe Thibault, Benoit Chabot
Little is known about how RNA binding proteins cooperate to control splicing, and how stress pathways reconfigure these assemblies to alter splice site selection. We have shown previously that SRSF10 plays an important role in the Bcl-x splicing response to DNA damage elicited by oxaliplatin in 293 cells. Here, RNA affinity assays using a portion of the Bcl-x transcript required for this response led to the recovery of the SRSF10-interacting protein 14-3-3ε and the Sam68-interacting protein hnRNP A1. Although SRSF10, 14-3-3ε, hnRNP A1/A2 and Sam68 do not make major contributions to the regulation of Bcl-x splicing under normal growth conditions, upon DNA damage they become important to activate the 5' splice site of pro-apoptotic Bcl-xS...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29344170/phosphorylation-of-ser6-in-hnrnpa1-by-s6k2-regulates-glucose-metabolism-and-cell-growth-in-colorectal-cancer
#6
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/29331391/microrna-mediated-regulation-of-splicing-factors-srsf1-srsf2-and-hnrnp-a1-in-context-of-their-alternatively-spliced-3-utrs
#7
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...
February 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29229447/hnrnp-a1-promotes-keratinocyte-cell-survival-post-uvb-radiation-through-pi3k-akt-mtor-pathway
#8
Jianguo Feng, Yi Liao, Xichao Xu, Qian Yi, Ling He, Liling Tang
hnRNP A1 acts as a critical splicing factor in regulating many alternative splicing events in various physiological and pathophysiological progressions. hnRNP A1 is capable of regulating UVB-induced hdm2 gene alternative splicing according to our previous study. However, the biological function and underlying molecular mechanism of hnRNP A1 in cell survival and cell cycle in response to UVB irradiation are still unclear. In this study, silencing hnRNP A1 expression by siRNA transfection led to decreased cell survival after UVB treatment, while promoting hnRNP A1 by lentiviruse vector resulted in increased cell survival...
January 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29165690/the-regulatory-g4-motif-of-the-kirsten-ras-kras-gene-is-sensitive-to-guanine-oxidation-implications-on-transcription
#9
Susanna Cogoi, Annalisa Ferino, Giulia Miglietta, Erik B Pedersen, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif...
January 25, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29161501/phenanthrene-induced-apoptosis-and-its-underlying-mechanism
#10
Xiangsheng Hong, Jianhui Qin, Rui Chen, Lilai Yuan, Jinmiao Zha, Chao Huang, Na Li, Xiaoya Ji, Zijian Wang
Phenanthrene (Phe) is one of the most abundant low-molecular-weight polycyclic aromatic hydrocarbons (PAHs). Widespread human and aquatic organism exposure to Phe has been reported, but the toxic effects of Phe and potential mechanisms are unclear. We focused on the chronic hepatotoxicity of Phe in adult Chinese rare minnows (Gobiocypris rarus) and the underlying mechanisms. The chronic effects of exposing Chinese rare minnows to 8.9, 82.3, or 510.0 μg/L Phe for 30 days were examined by histopathological observation, TUNEL assays, caspase activity assays, and gene expression profiles...
December 19, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29122468/an-intronic-variation-in-slc52a1-causes-exon-skipping-and-transient-riboflavin-responsive-multiple-acyl-coa-dehydrogenation-deficiency
#11
Signe Mosegaard, Gitte Hoffmann Bruun, Karen Freund Flyvbjerg, Yngve Thomas Bliksrud, Niels Gregersen, Maja Dembic, Ellen Annexstad, Trine Tangeraas, Rikke Katrine Jentoft Olsen, Brage S Andresen
Vitamin B2, riboflavin is essential for cellular function, as it participates in a diversity of redox reactions central to human metabolism, through its role as precursor for the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are electron carriers. The electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH), uses FAD as cofactor. The ETF and ETFDH are forming the electron transport pathway for many mitochondrial flavoprotein dehydrogenases involved in fatty acid, amino acid and choline metabolism...
December 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28985503/a-peptide-encoded-by-a-putative-lncrna-hoxb-as3-suppresses-colon-cancer-growth
#12
Jin-Zhou Huang, Min Chen, De Chen, Xing-Cheng Gao, Song Zhu, Hongyang Huang, Min Hu, Huifang Zhu, Guang-Rong Yan
A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28947773/anti-enterovirus-71-activities-of-melissa-officinalis-extract-and-its-biologically-active-constituent-rosmarinic-acid
#13
Sin-Guang Chen, Yann-Lii Leu, Mei-Ling Cheng, Siew Chin Ting, Ching-Chuan Liu, Shulhn-Der Wang, Cheng-Hung Yang, Cheng-Yu Hung, Hiroaki Sakurai, Kuan-Hsing Chen, Hung-Yao Ho
Enterovirus 71 (EV71) infection is endemic in the Asia-Pacific region. No specific antiviral drug has been available to treat EV71 infection. Melissa officinalis (MO) is a medicinal plant with long history of usage in the European and Middle East. We investigated whether an aqueous solution of concentrated methanolic extract (MOM) possesses antiviral activity. MOM inhibited plaque formation, cytopathic effect, and viral protein synthesis in EV71-infected cells. Using spectral techniques, we identified rosmarinic acid (RA) as a biologically active constituent of MOM...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903433/microrna-451-modulated-hnrnp-a1-takes-a-part-in-granulocytic-differentiation-regulation-and-acute-myeloid-leukemia
#14
Li Song, Hai-Shuang Lin, Jia-Nan Gong, Hua Han, Xiao-Shuang Wang, Rui Su, Ming-Tai Chen, Chao Shen, Yan-Ni Ma, Jia Yu, Jun-Wu Zhang
Myelopoiesis is under the control of a complex network containing various regulation factors. Deregulation of any important regulation factors may result in serious consequences including acute myeloid leukemia (AML). In order to find out the genes that may take a part in AML development, we analyzed data from AML cDNA microarray (GSE2191) in the NCBI data pool and noticed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is abnormally over-expressed in AML patients. Then we investigated the function and mechanisms of hnRNP A1 in myeloid development...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28802871/stack-locally-and-act-globally-a-few-nucleotides-make-all-the-difference-in-enterovirus-71-ires-binding-hnrnap-a1-and-infectious-phenotypes-commentary-on-hnrnp-a1-alters-the-structure-of-a-conserved-enterovirus-ires-domain-to-stimulate-viral-translation
#15
https://www.readbyqxmd.com/read/28762175/genetic-mutations-in-rna-binding-proteins-and-their-roles-in-als
#16
REVIEW
Katannya Kapeli, Fernando J Martinez, Gene W Yeo
Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of RNAs from synthesis to degradation. Hallmark features of RBPs in neuron dysfunction include misregulation of RNA processing, mislocalization of RBPs to the cytoplasm, and abnormal aggregation of RBPs. Much progress has been made in understanding how ALS-associated mutations in RBPs drive pathogenesis...
September 2017: Human Genetics
https://www.readbyqxmd.com/read/28746049/microrna-451-modulated-hnrnp-a1-takes-a-part-in-granulocytic-differentiation-regulation-and-acute-myeloid-leukemia
#17
Li Song, Hai-Shuang Lin, Jia-Nan Gong, Hua Han, Xiao-Shuang Wang, Rui Su, Ming-Tai Chen, Chao Shen, Yan-Ni Ma, Jia Yu, Jun-Wu Zhang
Myelopoiesis is under the control of a complex network containing various regulation factors. Deregulation of any important regulation factors may result in serious consequences including acute myeloid leukemia (AML). In order to find out the genes that may take a part in AML development, we analyzed data from AML cDNA microarray (GSE2191) in the NCBI data pool and noticed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is abnormally over-expressed in AML patients. Then we investigated the function and mechanisms of hnRNP A1 in myeloid development...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28650318/tandem-hnrnp-a1-rna-recognition-motifs-act-in-concert-to-repress-the-splicing-of-survival-motor-neuron-exon-7
#18
Irene Beusch, Pierre Barraud, Ahmed Moursy, Antoine Cléry, Frédéric Hai-Trieu Allain
HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28629158/contribution-of-the-degeneration-of-the-neuro-axonal-unit-to-the-pathogenesis-of-multiple-sclerosis
#19
REVIEW
Hannah E Salapa, Sangmin Lee, Yoojin Shin, Michael C Levin
Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. In recent years, it has become more evident that neurodegeneration, including neuronal damage and axonal injury, underlies permanent disability in MS. This manuscript reviews some of the mechanisms that could be responsible for neurodegeneration and axonal damage in MS and highlights the potential role that dysfunctional heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and antibodies to hnRNP A1 may play in MS pathogenesis...
June 18, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28625847/hnrnp-a1-alters-the-structure-of-a-conserved-enterovirus-ires-domain-to-stimulate-viral-translation
#20
Michele Tolbert, Christopher E Morgan, Marvin Pollum, Carlos E Crespo-Hernández, Mei-Ling Li, Gary Brewer, Blanton S Tolbert
Enteroviruses use a type I Internal Ribosome Entry Site (IRES) structure to facilitate protein synthesis and promote genome replication. Type I IRES elements require auxiliary host proteins to organize RNA structure for 40S ribosomal subunit assembly. Heterogeneous nuclear ribonucleoprotein A1 stimulates enterovirus 71 (EV71) translation in part through specific interactions with its stem loop II (SLII) IRES domain. Here, we determined a conjoined NMR-small angle x-ray scattering structure of the EV71 SLII domain and a mutant that significantly attenuates viral replication by abrogating hnRNP A1 interactions...
September 15, 2017: Journal of Molecular Biology
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