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https://www.readbyqxmd.com/read/27913144/effect-of-o-glcnacylation-on-hnrnp-a1-translocation-and-interaction-with-transportin1
#1
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...
November 29, 2016: 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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27867028/control-of-human-papillomavirus-gene-expression-by-alternative-splicing
#7
REVIEW
Sheila V Graham, Arwa Ali A Faizo
Human papillomaviruses possess circular double stranded DNA genomes of around 8kb in size from which multiple mRNAs are synthesized during an infectious life cycle. Although at least three viral promoters are used to initiate transcription, viral mRNAs are largely the product of processing of pre-mRNAs by alternative splicing and polyadenylation. The HPV life cycle and viral gene expression are tightly linked to differentiation of the epithelium the virus infects: there is an orchestrated production of viral mRNAs and proteins...
November 17, 2016: Virus Research
https://www.readbyqxmd.com/read/27851963/srsf10-connects-dna-damage-to-the-alternative-splicing-of-transcripts-encoding-apoptosis-cell-cycle-control-and-dna-repair-factors
#8
Lulzim Shkreta, Johanne Toutant, Mathieu Durand, James L Manley, Benoit Chabot
RNA binding proteins and signaling components control the production of pro-death and pro-survival splice variants of Bcl-x. DNA damage promoted by oxaliplatin increases the level of pro-apoptotic Bcl-xS in an ATM/CHK2-dependent manner, but how this shift is enforced is not known. Here, we show that in normally growing cells, when the 5' splice site of Bcl-xS is largely repressed, SRSF10 partially relieves repression and interacts with repressor hnRNP K and stimulatory hnRNP F/H proteins. Oxaliplatin abrogates the interaction of SRSF10 with hnRNP F/H and decreases the association of SRSF10 and hnRNP K with the Bcl-x pre-mRNA...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27824034/akap95-regulates-splicing-through-scaffolding-rnas-and-rna-processing-factors
#9
Jing Hu, Alireza Khodadadi-Jamayran, Miaowei Mao, Kushani Shah, Zhenhua Yang, Md Talat Nasim, Zefeng Wang, Hao Jiang
Alternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95, has a remarkable activity in enhancing chromatin transcription. In this study, we show that AKAP95 interacts with many factors involved in transcription and RNA processing, including selective groups of hnRNP proteins, through its N-terminal region, and directly regulates pre-mRNA splicing...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27808105/hnrnp-l-is-important-for-the-expression-of-oncogene-srsf3-and-oncogenic-potential-of-oral-squamous-cell-carcinoma-cells
#10
Rong Jia, Si Zhang, Miaomiao Liu, Yan Zhang, Yu Liu, Mingwen Fan, Jihua Guo
Oral squamous cell carcinoma (OSCC) is the leading cause of death related to oral diseases. The mechanisms of OSCC development remain largely unknown. Heterogeneous nuclear ribonucleoprotein L (HnRNP L) is a multi-functional splicing factor. It has been reported to be an important regulator of apoptosis. However, the functions of hnRNP L in cancer need to be further explored. In the present study, we found that OSCC tissues expressed significantly higher levels of hnRNP L than normal tissues. Depletion of hnRNP L retarded cell growth, cell migration, and tumorigenesis of OSCC cells...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27805251/in-silico-rna-seq-and-experimental-analyses-reveal-the-differential-expression-and-splicing-of-epdr1-and-znf518b-genes-in-relation-to-kras-mutations-in-colorectal-cancer-cells
#11
Ángela L Riffo-Campos, Josefa Castillo, Azahara Vallet-Sánchez, Guillermo Ayala, Andrés Cervantes, Gerardo López-Rodas, Luis Franco
Several drugs used for the treatment of colorectal cancer (CRC) are targeted at the epidermal growth factor receptor, but mutations in genes of the RAS family cause resistance to these drugs. Thus, extensive research is being carried out to counterbalance this resistance. The G13D mutation of KRAS is common in humans, and we previously reported that this mutation results in the epigenetic modification of hnRNP proteins, involved in RNA splicing. As aberrant splicing often results in oncogenicity, the present study aimed to identify the genes which show altered splicing patterns in connection with the G13D KRAS mutation...
October 27, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27793696/baseline-mapk-signaling-activity-confers-intrinsic-radioresistance-to-kras-mutant-colorectal-carcinoma-cells-by-rapid-upregulation-of-heterogeneous-nuclear-ribonucleoprotein-k-hnrnp-k
#12
Stefan Eder, Annette Arndt, Andreas Lamkowski, Wassiliki Daskalaki, Alexis Rump, Markus Priller, Felicitas Genze, Eva Wardelmann, Matthias Port, Konrad Steinestel
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is overexpressed in malignant tumors and involved in DNA damage response upon ionizing radiation (IR). Here, we investigate its role in radioresistance of colorectal carcinoma (CRC) and evaluate a pharmacological approach to enhance CRC radiosensitivity via downregulation of hnRNP K. We show that hnRNP K is overexpressed in CRC tissue specimens and upregulated in response to IR in vitro, which occurs faster in KRAS-mutant CRC cells. HnRNP K knockdown impairs cell survival, cell cycle progression and KRAS-dependent radioresistance and increases apoptosis...
October 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27773581/protein-rna-networks-regulated-by-normal-and-als-associated-mutant-hnrnpa2b1-in-the-nervous-system
#13
Fernando J Martinez, Gabriel A Pratt, Eric L Van Nostrand, Ranjan Batra, Stephanie C Huelga, Katannya Kapeli, Peter Freese, Seung J Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C Wang, Julia K Nussbacher, Sara M Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C Frank Bennett, Manuel Ares, Christopher B Burge, J Paul Taylor, Frank Rigo, Gene W Yeo
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism...
November 23, 2016: Neuron
https://www.readbyqxmd.com/read/27754128/os-25-03-overexpression-of-heterogeneous-nuclear-ribonucleoprotein-f-prevents-systemic-hypertension-and-kidney-injury-and-normalizes-renal-renin-angiotensin-system-genes-expression-in-type-2-diabetic-db-db-transgenic-mice
#14
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27741228/correction-hnrnp-k-coordinates-transcriptional-silencing-by-setdb1-in-embryonic-stem-cells
#15
Peter J Thompson, Vered Dulberg, Kyung-Mee Moon, Leonard J Foster, Carol Chen, Mohammad M Karimi, Matthew C Lorincz
[This corrects the article DOI: 10.1371/journal.pgen.1004933.].
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27732855/the-rna-binding-protein-syncrip-is-a-component-of-the-hepatocyte-exosomal-machinery-controlling-microrna-sorting
#16
Laura Santangelo, Giorgio Giurato, Carla Cicchini, Claudia Montaldo, Carmine Mancone, Roberta Tarallo, Cecilia Battistelli, Tonino Alonzi, Alessandro Weisz, Marco Tripodi
Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27699280/ptb-and-tiar-binding-to-insulin-mrna-3-and-5-utrs-implications-for-insulin-biosynthesis-and-messenger-stability
#17
Rikard G Fred, Syrina Mehrabi, Christopher M Adams, Nils Welsh
OBJECTIVES: Insulin expression is highly controlled on the posttranscriptional level. The RNA binding proteins (RBPs) responsible for this result are still largely unknown. METHODS AND RESULTS: To identify RBPs that bind to insulin mRNA we performed mass spectrometry analysis on proteins that bound synthetic oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat and human insulin mRNA in vitro. We observed that the RBPs heterogeneous nuclear ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L and T-cell restricted intracellular antigen 1-related protein (TIA-1-related protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3-isobutyl-1-methylxanthine (IBMX) or nitric oxide...
September 2016: Heliyon
https://www.readbyqxmd.com/read/27683223/chtop-chromatin-target-of-prmt1-auto-regulates-its-expression-level-via-intron-retention-and-nonsense-mediated-decay-of-its-own-mrna
#18
Keiichi Izumikawa, Harunori Yoshikawa, Hideaki Ishikawa, Yuko Nobe, Yoshio Yamauchi, Sjaak Philipsen, Richard J Simpson, Toshiaki Isobe, Nobuhiro Takahashi
Chtop (chromatin target of Prmt1) regulates various aspects of gene expression including transcription and mRNA export. Despite these important functions, the regulatory mechanism underlying Chtop expression remains undetermined. Using Chtop-expressing human cell lines, we demonstrate that Chtop expression is controlled via an autoregulatory negative feedback loop whereby Chtop binds its own mRNA to retain intron 2 during splicing; a premature termination codon present at the 5' end of intron 2 leads to nonsense-mediated decay of the mRNA...
November 16, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27669098/a-mechanosensor-mechanism-controls-the-g-quadruplex-i-motif-molecular-switch-in-the-myc-promoter-nhe-iii1
#19
Caleb Sutherland, Yunxi Cui, Hanbin Mao, Laurence H Hurley
MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G-quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation...
October 11, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27663142/rna-binding-disturbances-as-a-continuum-from-spinocerebellar-ataxia-type-2-to-parkinson-disease
#20
Aurore Nkiliza, Eugénie Mutez, Clémence Simonin, Frédéric Leprêtre, Aurélie Duflot, Martin Figeac, Céline Villenet, Pierre Semaille, Thomas Comptdaer, Alexandre Genet, Bernard Sablonnière, David Devos, Luc Defebvre, Alain Destée, Marie-Christine Chartier-Harlin
CAG triplet expansions in Ataxin-2 gene (ATXN2) cause spinocerebellar ataxia type 2 and have a role that remains to be clarified in Parkinson's disease (PD). To study the molecular events associated with these expansions, we sequenced them and analyzed the transcriptome from blood cells of controls and three patient groups diagnosed with spinocerebellar ataxia type 2 (herein referred to as SCA2c) or PD with or without ATXN2 triplet expansions (named SCA2p). The transcriptome profiles of these 40 patients revealed three main observations: i) a specific pattern of pathways related to cellular contacts, proliferation and differentiation associated with SCA2p group, ii) similarities between the SCA2p and sporadic PD groups in genes and pathways known to be altered in PD such as Wnt, Ephrin and Leukocyte extravasation signaling iii) RNA metabolism disturbances with "RNA-binding" and "poly(A) RNA-binding" as a common feature in all groups...
September 20, 2016: Neurobiology of Disease
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