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HnRNP A1

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https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#1
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
#2
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
#3
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
#4
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
#5
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-tumour-suppressor-splice-variant-of-the-oncogene-her2-regulated
#6
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
#7
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
#8
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
#9
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/27880931/an-xist-related-small-rna-regulates-kras-g-quadruplex-formation-beyond-x-inactivation
#10
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/27613566/hnrnp-a1-antagonizes-cellular-senescence-and-senescence-associated-secretory-phenotype-via-regulation-of-sirt1-mrna-stability
#11
Hui Wang, Limin Han, Ganye Zhao, Hong Shen, Pengfeng Wang, Zhaomeng Sun, Chenzhong Xu, Yuanyuan Su, Guodong Li, Tanjun Tong, Jun Chen
Senescent cells display a senescence-associated secretory phenotype (SASP) which contributes to tumor suppression, aging, and cancer. However, the underlying mechanisms for SASP regulation are not fully elucidated. SIRT1, a nicotinamide adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism, inflammatory response, and longevity, etc. However, its posttranscriptional regulation and its roles in cellular senescence and SASP regulation are still elusive. Here, we identify the RNA-binding protein hnRNP A1 as a posttranscriptional regulator of SIRT1, as well as cell senescence and SASP regulator...
September 9, 2016: Aging Cell
https://www.readbyqxmd.com/read/27595546/the-prevalent-deep-intronic-c-639-919-g-a-gla-mutation-causes-pseudoexon-activation-and-fabry-disease-by-abolishing-the-binding-of-hnrnpa1-and-hnrnp-a2-b1-to-a-splicing-silencer
#12
Bruno Palhais, Maja Dembic, Rugivan Sabaratnam, Kira S Nielsen, Thomas Koed Doktor, Gitte Hoffmann Bruun, Brage Storstein Andresen
Fabry disease is an X-linked recessive inborn disorder of the glycosphingolipid metabolism, caused by total or partial deficiency of the lysosomal α-galactosidase A enzyme due to mutations in the GLA gene. The prevalent c.639+919 G>A mutation in GLA leads to pathogenic insertion of a 57bp pseudoexon sequence from intron 4, which is responsible for the cardiac variant phenotype. In this study we investigate the splicing regulatory mechanism leading to GLA pseudoexon activation. Splicing analysis of GLA minigenes revealed that pseudoexon activation is influenced by cell-type...
August 27, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27567428/apolipoprotein-a1-and-heterogeneous-nuclear-ribonucleoprotein-e1-implicated-in-the-regulation-of-embryo-implantation-by-inhibiting-lipid-peroxidation
#13
Jia Jia, Jinhai Gou, Xia Zhao, Tao Yi, Zhengyu Li
It is known that apolipoprotein A1 (apoA1) is a stimulator of endothelial nitric oxide synthase (eNOS), and that heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1)-containing RNP complexes is a key protector of basal stabilization of eNOS mRNA. Recently, we found that apoA1 and hnRNP-E1 were up-regulated during peri-implantation period, and the purpose of this study was to explore the roles of apoA1 and hnRNP-E1 during this period in the mouse. It was found that the up-regulation of apoA1 and hnRNP-E1 were dependent on the presence and status of blastocysts, on endometrial decidualization and on the progesterone and 17β-oestradiol status...
August 18, 2016: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27500866/the-presence-of-heterogeneous-nuclear-ribonucleoproteins-in-frontotemporal-lobar-degeneration-with-fus-positive-inclusions
#14
Priya Gami-Patel, Rina Bandopadhyay, Jack Brelstaff, Tamas Revesz, Tammaryn Lashley
Frontotemporal lobar degeneration with fused in sarcoma-positive inclusions (FTLD-FUS) is a disease with unknown cause. Transportin 1 is abundantly found in FUS-positive inclusions and responsible for the nuclear import of the FET proteins of which FUS is a member. The presence of all FET proteins in pathological inclusions suggests a disturbance of transportin 1-mediated nuclear import. FUS also belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. We investigated whether hnRNP proteins are associated with FUS pathology implicating dysfunctional nuclear export in the pathogenesis of FTLD-FUS...
October 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27489271/serine-arginine-rich-splicing-factor-3-and-heterogeneous-nuclear-ribonucleoprotein-a1-regulate-alternative-rna-splicing-and-gene-expression-of-human-papillomavirus-18-through-two-functionally-distinguishable-cis-elements
#15
Masahiko Ajiro, Shuang Tang, John Doorbar, Zhi-Ming Zheng
UNLABELLED: Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type associated with cervical, anogenital, and oropharyngeal cancers. Like other oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic pre-mRNAs that are regulated by alternative RNA splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. However, RNA cis-regulatory elements and trans-acting factors contributing to HPV18 alternative RNA splicing remain unknown...
October 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27449854/autoantibodies-to-heterogeneous-nuclear-ribonuclear-protein-a1-hnrnpa1-cause-altered-ribostasis-and-neurodegeneration-the-legacy-of-ham-tsp-as-a-model-of-progressive-multiple-sclerosis
#16
Michael C Levin, Sangmin Lee, Lidia A Gardner, Yoojin Shin, Joshua N Douglas, Hannah Salapa
Several years following its discovery in 1980, infection with human T-lymphotropic virus type 1 (HTLV-1) was shown to cause HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease biologically similar to progressive forms of multiple sclerosis (MS). In this manuscript, we review some of the clinical, pathological, and immunological similarities between HAM/TSP and MS with an emphasis on how autoantibodies to an RNA binding protein, heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), might contribute to neurodegeneration in immune mediated diseases of the central nervous system...
July 17, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27437398/crystal-structure-of-the-n-terminal-rna-recognition-motif-of-mrna-decay-regulator-auf1
#17
Young Jun Choi, Je-Hyun Yoon, Jeong Ho Chang
AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3'-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27402862/poly-adp-ribosyl-ation-of-hnrnp-a1-protein-controls-translational-repression-in-drosophila
#18
Yingbiao Ji, Alexei V Tulin
Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) regulates the posttranscriptional fate of RNA during development. Drosophila hnRNP A1, Hrp38, is required for germ line stem cell maintenance and oocyte localization. The mRNA targets regulated by Hrp38 are mostly unknown. We identified 428 Hrp38-associated gene transcripts in the fly ovary, including mRNA of the translational repressor Nanos. We found that Hrp38 binds to the 3' untranslated region (UTR) of Nanos mRNA, which contains a translation control element...
October 1, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27391474/antibodies-to-the-rna-binding-protein-hnrnp-a1-contribute-to-neurodegeneration-in-a-model-of-central-nervous-system-autoimmune-inflammatory-disease
#19
Joshua N Douglas, Lidia A Gardner, Hannah E Salapa, Stephen J Lalor, Sangmin Lee, Benjamin M Segal, Paul E Sawchenko, Michael C Levin
BACKGROUND: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration in multiple sclerosis is the targeting of neuronal and axonal antigens by autoantibodies. Multiple sclerosis patients develop antibodies to the RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which is enriched in neurons...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27380775/global-identification-of-hnrnp-a1-binding-sites-for-sso-based-splicing-modulation
#20
Gitte H Bruun, Thomas K Doktor, Jonas Borch-Jensen, Akio Masuda, Adrian R Krainer, Kinji Ohno, Brage S Andresen
BACKGROUND: Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif...
2016: BMC Biology
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