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HnRNP A1

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https://www.readbyqxmd.com/read/28446664/analysis-of-competing-hiv-1-splice-donor-sites-uncovers-a-tight-cluster-of-splicing-regulatory-elements-within-exon-2-2b
#1
Anna-Lena Brillen, Lara Walotka, Frank Hillebrand, Lisa Müller, Marek Widera, Stephan Theiss, Heiner Schaal
The HIV-1 accessory protein Vif is essential for viral replication by counteracting the host restriction factor APOBEC3G (A3G), and balanced levels of both proteins are required for efficient viral replication. Non-coding exons 2/2b contain the Vif start codon between their alternatively used splice donors 2 and 2b (D2 and D2b). For the vif mRNA, intron 1 must be removed, while intron 2 must be retained. Thus, splice acceptor 1 (A1) must be activated by U1 snRNP binding to either D2 or D2b, while splicing at D2 or D2b must be prevented...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28431575/heterogeneous-ribonuclear-protein-a3-hnrnp-a3-is-present-in-dipeptide-repeat-protein-containing-inclusions-in-frontotemporal-lobar-degeneration-and-motor-neurone-disease-associated-with-expansions-in-c9orf72-gene
#2
Yvonne S Davidson, Louis Flood, Andrew C Robinson, Yoshihiro Nihei, Kohji Mori, Sara Rollinson, Anna Richardson, Bridget C Benson, Matthew Jones, Julie S Snowden, Stuart Pickering-Brown, Christian Haass, Tammaryn Lashley, David M A Mann
Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter behaviour, personality and language. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those without known mutation...
April 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28428548/antiviral-activities-of-schizonepeta-tenuifolia-briq-against-enterovirus-71-in-vitro-and-in-vivo
#3
Sin-Guang Chen, Mei-Ling Cheng, Kuan-Hsing Chen, Jim-Tong Horng, Ching-Chuan Liu, Shih-Min Wang, Hiroaki Sakurai, Yann-Lii Leu, Shulhn-Der Wang, Hung-Yao Ho
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379492/identification-and-dynamic-changes-of-rnas-isolated-from-raly-containing-ribonucleoprotein-complexes
#4
Annalisa Rossi, Albertomaria Moro, Toma Tebaldi, Nicola Cornella, Lisa Gasperini, Lorenzo Lunelli, Alessandro Quattrone, Gabriella Viero, Paolo Macchi
RALY is a member of the heterogeneous nuclear ribonucleoprotein family (hnRNP), a large family of RNA-binding proteins involved in many aspects of RNA metabolism. Although RALY interactome has been recently characterized, a comprehensive global analysis of RALY-associated RNAs is lacking and the biological function of RALY remains elusive. Here, we performed RIP-seq analysis to identify RALY interacting RNAs and assessed the role of RALY in gene expression. We demonstrate that RALY binds specific coding and non-coding RNAs and associates with translating mRNAs of mammalian cells...
April 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28368279/crystal-structure-of-the-human-heterogeneous-ribonucleoprotein-a18-rna-recognition-motif
#5
Katherine Coburn, Zephan Melville, Ehson Aligholizadeh, Braden M Roth, Kristen M Varney, France Carrier, Edwin Pozharski, David J Weber
The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growth via the coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e. hnRNP A1), three residues on one face of an antiparallel β-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein-nucleic acid interactions...
April 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28315432/splicing-factors-of-sr-and-hnrnp-families-as-regulators-of-apoptosis-in-cancer
#6
Hanna Kędzierska, Agnieszka Piekiełko-Witkowska
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28220845/heterogeneous-nuclear-ribonucleoprotein-a1-regulates-rhythmic-synthesis-of-mouse-nfil3-protein-via-ires-mediated-translation
#7
Hyo-Jin Kim, Hwa-Rim Lee, Ji-Young Seo, Hye Guk Ryu, Kyung-Ha Lee, Do-Yeon Kim, Kyong-Tai Kim
Nuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5'-untranslated region (5'-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193894/rules-of-rna-specificity-of-hnrnp-a1-revealed-by-global-and-quantitative-analysis-of-its-affinity-distribution
#8
Niyati Jain, Hsuan-Chun Lin, Christopher E Morgan, Michael E Harris, Blanton S Tolbert
Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a multipurpose RNA-binding protein (RBP) involved in normal and pathological RNA metabolism. Transcriptome-wide mapping and in vitro evolution identify consensus hnRNP A1 binding motifs; however, such data do not reveal how surrounding RNA sequence and structural context modulate affinity. We determined the affinity of hnRNP A1 for all possible sequence variants (n = 16,384) of the HIV exon splicing silencer 3 (ESS3) 7-nt apical loop. Analysis of the affinity distribution identifies the optimal motif 5'-YAG-3' and shows how its copy number, position in the loop, and loop structure modulate affinity...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28186082/both-sides-of-the-same-coin-rac1-splicing-regulating-by-egf-signaling
#9
Xiang-Dong Fu
EGF, a well-studied mitogen for cancer cells, is revealed to induce an E3 ubiquitin ligase adaptor SPSB1, which recruits the Elongin B/C-Collin complex to trigger ubiquitylation of the negative splicing regulator hnRNP A1. This event is synergized with EGF-activated SR proteins to alter alternative splicing of a key small GTPase Rac1 to enhance cell migration, highlighting converging EGF signals on both negative and positive splicing regulators to jointly promote a key cancer pathway.
April 2017: Cell Research
https://www.readbyqxmd.com/read/28152480/securinine-enhances-smn2-exon-7-inclusion-in-spinal-muscular-atrophy-cells
#10
Yu-Chia Chen, Jan-Gowth Chang, Ting-Yuan Liu, Yuh-Jyh Jong, Wei-Lin Cheng, Chung-Yee Yuo
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron gene (SMN1) on chromosome 5q13. A second copy of the SMN gene (SMN2) also exists on chromosome 5, and both genes can produce functional protein. However, due to alternative splicing of the exon 7, the majority of SMN protein produced by SMN2 is truncated and unable to compensate for the loss of SMN1...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28115626/prmt5-regulates-ires-dependent-translation-via-methylation-of-hnrnp-a1
#11
Guozhen Gao, Surbhi Dhar, Mark T Bedford
The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES)...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#12
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28077597/muscle-developmental-defects-in-heterogeneous-nuclear-ribonucleoprotein-a1-knockout-mice
#13
Ting-Yuan Liu, Yu-Chia Chen, Yuh-Jyh Jong, Huai-Jen Tsai, Chien-Chin Lee, Ya-Sian Chang, Jan-Gowth Chang, Yung-Fu Chang
Heterogeneous ribonucleoprotein A1 (hnRNP A1) is crucial for regulating alternative splicing. Its integrated function within an organism has not, however, been identified. We generated hnRNP A1 knockout mice to study the role of hnRNP A1 in vivo The knockout mice, hnRNP A1(-/-), showed embryonic lethality because of muscle developmental defects. The blood pressure and heart rate of the heterozygous mice were higher than those of the wild-type mice, indicating heart function defects. We performed mouse exon arrays to study the muscle development mechanism...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28076796/ribosomal-proteins-rpl22-and-rpl22l1-control-morphogenesis-by-regulating-pre-mrna-splicing
#14
Yong Zhang, Monique N O'Leary, Suraj Peri, Minshi Wang, Jikun Zha, Simon Melov, Dietmar J Kappes, Qing Feng, Jennifer Rhodes, Paul S Amieux, David R Morris, Brian K Kennedy, David L Wiest
Most ribosomal proteins (RP) are regarded as essential, static components that contribute only to ribosome biogenesis and protein synthesis. However, emerging evidence suggests that RNA-binding RP are dynamic and can influence cellular processes by performing "extraribosomal," regulatory functions involving binding to select critical target mRNAs. We report here that the RP, Rpl22, and its highly homologous paralog Rpl22-Like1 (Rpl22l1 or Like1) play critical, extraribosomal roles in embryogenesis. Indeed, they antagonistically control morphogenesis through developmentally regulated localization to the nucleus, where they modulate splicing of the pre-mRNA encoding smad2, an essential transcriptional effector of Nodal/TGF-β signaling...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28000042/hnrnpa1-autoregulates-its-own-mrna-expression-to-remain-non-cytotoxic
#15
Hiroaki Suzuki, Masaaki Matsuoka
Heterogeneous nuclear ribonucleoprotein (hnRNP)A1, a member of the hnRNP family, is involved in a variety of RNA metabolisms. The hnRNPA1 expression is altered in some human diseases and mutations of the hnRNPA1 gene cause amyotrophic lateral sclerosis and multisystem proteinopathy. It has been therefore assumed that the dysregulation of hnRNPA1 is linked to the pathogenesis of the diseases. However, the mechanism underlying the regulation of the hnRNPA1 expression remains unknown. In this study, using cell-based models, we have found that hnRNPA1 negatively regulates its own mRNA expression by inhibiting the intron10 splicing of hnRNPA1 pre-mRNA...
March 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27979648/methylarginines-within-the-rgg-motif-region-of-hnrnp-a1-affect-its-ires-trans-acting-factor-activity-and-are-required-for-hnrnp-a1-stress-granule-localization-and-formation
#16
Michael L Wall, Stephen M Lewis
Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a stress granule-associated RNA-binding protein that plays a role in apoptosis and cellular stress recovery. HnRNP A1 is a major non-histone target of protein arginine methyltransferase 1, which asymmetrically dimethylates hnRNP A1 at several key arginine residues within its arginine-glycine-glycine (RGG)-motif region. Although arginine methylation is known to regulate general RNA binding of hnRNP A1 in vitro, the functional role of arginine methylation in hnRNP A1 cytoplasmic activity is unknown...
December 13, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27935425/how-is-herstatin-a-tumor-suppressor-splice-variant-of-the-oncogene-her2-regulated
#17
Marco Silipo, Hannah Gautrey, Swapna Satam, Thomas Lennard, Alison Tyson-Capper
The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is overexpressed in 20-30% of breast tumors leading to faster growing and more aggressive tumors. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumor suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin...
December 9, 2016: RNA Biology
https://www.readbyqxmd.com/read/27919832/differential-hnrnp-d-isoform-incorporation-may-confer-plasticity-to-the-essv-mediated-repressive-state-across-hiv-1-exon-3
#18
Frank Hillebrand, Jan Otto Peter, Anna-Lena Brillen, Marianne Otte, Heiner Schaal, Steffen Erkelenz
Even though splicing repression by hnRNP complexes bound to exonic sequences is well-documented, the responsible effector domains of hnRNP proteins have been described for only a select number of hnRNP constituents. Thus, there is only limited information available for possible varying silencer activities amongst different hnRNP proteins and composition changes within possible hnRNP complex assemblies. In this study, we identified the glycine-rich domain (GRD) of hnRNP proteins as a unifying feature in splice site repression...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913144/the-effect-of-o-glcnacylation-on-hnrnp-a1-translocation-and-interaction-with-transportin1
#19
Shira Roth, Isam Khalaila
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27888145/critical-role-of-hnrnp-a1-in-activating-kras-transcription-in-pancreatic-cancer-cells-a-molecular-mechanism-involving-g4-dna
#20
REVIEW
Susanna Cogoi, Valentina Rapozzi, Sabina Cauci, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. Its crucial role in the tumourigenesis of pancreatic ductal adenocarcinoma (PDAC) has been widely demonstrated. As this deadly cancer does not sufficiently respond to conventional chemotherapies, it is important to increase our knowledge of pancreatic cancer biology, in particular how oncogenic KRAS is regulated. The promoter of KRAS contains a GA-element composed of runs of guanines that fold into a G4 structure. This unusual DNA conformation is recognized by several nuclear proteins, including MAZ and hnRNP A1...
November 22, 2016: Biochimica et Biophysica Acta
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