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https://www.readbyqxmd.com/read/28088793/hnrnp-l-mediates-bladder-cancer-progression-by-inhibiting-apoptotic-signaling-and-enhancing-mapk-signaling-pathways
#1
Daojun Lv, Huayan Wu, Rongwei Xing, Fangpeng Shu, Bin Lei, Chengyong Lei, Xumin Zhou, Bo Wan, Yu Yang, Liren Zhong, Xiangming Mao, Yaguang Zou
Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration...
January 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#2
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/28079881/translational-upregulation-of-aurora-a-by-hnrnp-q1-contributes-to-cell-proliferation-and-tumorigenesis-in-colorectal-cancer
#3
Chien-Hsien Lai, Yu-Chuan Huang, Jenq-Chang Lee, Joseph Ta-Chien Tseng, Kung-Chao Chang, Yen-Ju Chen, Nai-Jhu Ding, Pao-Hsuan Huang, Wen-Chang Chang, Bo-Wen Lin, Ruo-Yu Chen, Yu-Chu Wang, Yi-Chien Lai, Liang-Yi Hung
By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077597/muscle-developmental-defects-in-heterogeneous-nuclear-ribonucleoprotein-a1-knockout-mice
#4
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
#5
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/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#6
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28038443/hnrnp-l-promotes-prostate-cancer-progression-by-enhancing-cell-cycling-and-inhibiting-apoptosis
#7
Xumin Zhou, Qi Li, Jincan He, Liren Zhong, Fangpeng Shu, Rongwei Xing, Daojun Lv, Bin Lei, Bo Wan, Yu Yang, Huayan Wu, Xiangming Mao, Yaguang Zou
Expression of the RNA-binding protein HnRNP-L was previously shown to associate with tumorigenesis in liver and lung cancer. In this study, we examined the role of HnRNP-L in prostate cancer (Pca). We found that HnRNP-L is overexpressed in prostate tissue samples from 160 PC patients compared with tissue samples from 32 donors with cancers other than Pca. Moreover, HnRNP-L positively correlated with aggressive tumor characteristics. HnRNP-L knockdown inhibited cell proliferation and promoted cell apoptosis of Pca cell lines in vitro, and suppressed tumor growth when the cells were subcutaneously implanted in an athymic mouse model...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031331/activation-dependent-traf3-exon-8-alternative-splicing-is-controlled-by-celf2-and-hnrnp-c-binding-to-an-upstream-intronic-element
#8
Astrid-Solveig Schultz, Marco Preußner, Mario Bunse, Rotem Karni, Florian Heyd
Cell-type specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates non-canonical NFkB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify cis- and trans-regulatory elements rendering this splicing switch activation-dependent and cell-type specific...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28024474/-hnrnp-k-contributes-to-adriamycin-resistance-in-acute-myeloid-leukemia-through-regulating-autophagy
#9
Jin-Fang Zhang, Xiao-Li Liu, Yu-Deng Lin, Yu-Ling Li, Jian-Wei Pan, Sa Zong, Yang Zhou
OBJECTIVE: To explore the role of heterogeneous nuclear ribonucleoprotein(hnRNP) K regulating autophagy in the drug resistance of acute myeloid leukemia, so as to provide a new molecular marker for treatment of leukemia. METHODS: The relationship between the expression level of hnRNP K and the drug resistance of myeloid leukemia was verified by fluorescence quantitative PCR; the expression of autophagy related protein LC3I/ II was detected by Western blot after the hnRNP K was modulated by RNA interference technology; the sensitivity of leukemia cells to doxorubicin was analyzed before and after the expression of hnRNP K were modulatd...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28000042/hnrnpa1-autoregulates-its-own-mrna-expression-to-remain-non-cytotoxic
#10
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...
December 20, 2016: 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
#11
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/27940037/the-g-quadruplex-specific-rna-helicase-dhx36-regulates-p53-pre-mrna-3-end-processing-following-uv-induced-dna-damage
#12
Michelle Newman, Rym Sfaxi, Abhijit Saha, David Monchaud, Marie-Paule Teulade-Fichou, Stéphan Vagner
Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage response leading to a profound impact on the level of protein expression since unprocessed transcripts at the 3'-end will be degraded or unable to be transported to the cytoplasm. However, a compensatory mechanism involving the binding of the hnRNP H/F family of RNA binding proteins to an RNA G-quadruplex (G4) structure located in the vicinity of a polyadenylation site has previously been described to allow the transcript encoding the p53 tumour suppressor protein to be properly processed during DNA damage and to provide the cells with a way to react to DNA damage...
December 7, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27935425/how-is-herstatin-a-tumour-suppressor-splice-variant-of-the-oncogene-her2-regulated
#13
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 over-expressed in 20-30% of breast tumours leading to faster growing and more aggressive tumours. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumour 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
#14
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
#15
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/27897116/the-molecular-mechanisms-and-the-role-of-hnrnp-k-protein-post-translational-modification-in-dna-damage-repair
#16
Jing Lu, Feng-Hou Gao
DNA damage repair is a kind of cellular self-protection mechanism that some relevant proteins are activated when DNA damage response happens in order to maintain the intracellular function stability and structure integrity. Post-translational modifications (PTMs) of proteins can rapidly confers to them more complicated structure and sophisticated function by covalently combining with different small molecules with target proteins, which in turn plays an important regulatory role in DNA damage repair. It was reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) could be involved in DNA damage repair process under the regulation of its many post-translational modifications, including methylation, ubiquitination, sumoylation and phosphorylation...
November 29, 2016: Current Medicinal Chemistry
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
#17
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
https://www.readbyqxmd.com/read/27882870/large-scale-remodeling-of-a-repressed-exon-ribonucleoprotein-to-an-exon-definition-complex-active-for-splicing
#18
Somsakul Pop Wongpalee, Ajay Vashisht, Shalini Sharma, Darryl Chui, James A Wohlschlegel, Douglas L Black
Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition...
November 24, 2016: ELife
https://www.readbyqxmd.com/read/27880931/an-xist-related-small-rna-regulates-kras-g-quadruplex-formation-beyond-x-inactivation
#19
Yuli C Chang, Chien-Chih Chiu, Chung-Yee Yuo, Wen-Ling Chan, Ya-Sian Chang, Wen-Hsin Chang, Shou-Mei Wu, Han-Lin Chou, Ta-Chih Liu, Chi-Yu Lu, Wen-Kuang Yang, Jan-Gowth Chang
X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for the initiation of X-chromosome inactivation. However, little is known about other roles of XIST in the physiological process in eukaryotic cells. In this study, the bioinformatics approaches revealed XIST could be processed into a small non-coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its expression was gender-independent, suggesting the role of XPi2 was beyond X-chromosome inactivation. The pull-down assay combined with LC-MS-MS identified two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation of G-quadruplex...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27871485/unusual-processing-generates-spa-lncrnas-that-sequester-multiple-rna-binding-proteins
#20
Huang Wu, Qing-Fei Yin, Zheng Luo, Run-Wen Yao, Chuan-Chuan Zheng, Jun Zhang, Jian-Feng Xiang, Li Yang, Ling-Ling Chen
We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3' processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5' end, and allows continuous Pol II elongation...
November 3, 2016: Molecular Cell
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