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HnRNP A1

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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
#1
https://www.readbyqxmd.com/read/28762175/genetic-mutations-in-rna-binding-proteins-and-their-roles-in-als
#2
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...
July 31, 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
#3
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
#4
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
#5
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
#6
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...
June 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28600288/tcr-signal-strength-regulates-akt-substrate-specificity-to-induce-alternate-murine-th-and-t-regulatory-cell-differentiation-programs
#7
William F Hawse, William C Boggess, Penelope A Morel
The Akt/mTOR pathway is a key driver of murine CD4(+) T cell differentiation, and induction of regulatory T (Treg) cells results from low TCR signal strength and low Akt/mTOR signaling. However, strong TCR signals induce high Akt activity that promotes Th cell induction. Yet, it is unclear how Akt controls alternate T cell fate decisions. We find that the strength of the TCR signal results in differential Akt enzymatic activity. Surprisingly, the Akt substrate networks associated with T cell fate decisions are qualitatively different...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28560430/fyn-heterogeneous-nuclear-ribonucleoprotein-e1-signaling-regulates-pancreatic-cancer-metastasis-by-affecting-the-alternative-splicing-of-integrin-%C3%AE-1
#8
Peng Jiang, Zhonghu Li, Feng Tian, Xiaowu Li, Jin Yang
Pancreatic cancer is characterized by a dense desmoplastic reaction in which extracellular matrix proteins accumulate and surround tumor cells. Integrins and their related signaling molecules are associated with progression of pancreatic cancer. In the present study, the association between the metastasis of pancreatic cancer and the expression of hnRNP E1 and integrin β1 was evaluated. In vitro and in vivo experiments were designed to study the mechanism underlying the regulation of integrin β1 splicing by the Fyn/hnRNP E1 spliceosome...
July 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28510424/structure-dependent-binding-of-hnrnpa1-to-telomere-rna
#9
Xiao Liu, Takumi Ishizuka, Hong-Liang Bao, Kei Wada, Yuma Takeda, Keisuke Iida, Kazuo Nagasawa, Danzhou Yang, Yan Xu
Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an RNA-binding protein involved in the telomere maintenance machinery. To date, little is known about how hnRNPA1 binds to telomeric RNA. In this study, we investigated the binding affinity and recognition mechanism of telomere RNA with the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking method, we showed that the telomere RNA G-quadruplex with loops is important in the interaction of telomere RNA with hnRNPA1...
June 7, 2017: Journal of the American Chemical Society
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
#10
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. Noncoding exons 2/2b contain the Vif start codon between their alternatively used splice donors 2 and 2b (D2 and D2b). For 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...
July 15, 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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)...
May 5, 2017: Nucleic Acids Research
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