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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
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
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
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...
January 10, 2018: Experimental Cell Research
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
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...
November 20, 2017: Nucleic Acids Research
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
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
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
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
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
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
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
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
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
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
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
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
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
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