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https://www.readbyqxmd.com/read/28284018/chemical-shift-assignments-of-the-first-and-second-rrms-of-nrd1-a-fission-yeast-mapk-target-rna-binding-protein
#1
Ayaho Kobayashi, Teppei Kanaba, Ryosuke Satoh, Yutaka Ito, Reiko Sugiura, Masaki Mishima
Negative regulator differentiation 1 (Nrd1), a fission yeast RNA binding protein, modulates cytokinesis and sexual development and contributes to stress granule formation in response to environmental stresses. Nrd1 comprises four RRM domains and binds and stabilizes Cdc4 mRNA that encodes the myosin II light chain. Nrd1 binds the Cpc2 fission-yeast RACK1 homolog, and the interaction promotes Nrd1 localization to stress granules. Interestingly, Pmk1 mitogen-activated protein kinase phosphorylates Thr40 in the unstructured N-terminal region and Thr126 in the first RRM domain of Nrd1...
March 11, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#2
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28263595/enhanced-binding-affinity-for-an-i-motif-dna-substrate-exhibited-by-a-protein-containing-nucleobase-amino-acids
#3
Xiaoguang Bai, Poulami Talukder, Sasha M Daskalova, Basab Roy, Shengxi Chen, Zhongxian Li, Larisa M Dedkova, Sidney M Hecht
Several variants of a nucleic acid binding motif (RRM1) of putative transcription factor hnRNP LL containing nucleobase amino acids at specific positions have been prepared and used to study binding affinity for the BCL2 i-motif DNA. Molecular modeling suggested a number of amino acids in RRM1 likely to be involved in interaction with the i-motif DNA, and His24 and Arg26 were chosen for modification based on their potential ability to interact with G14 of the i-motif DNA. Four nucleobase amino acids were introduced into RRM1 at one or both of positions 24 and 26...
March 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28263231/appendix-derived-pseudomyxoma-peritonei-pmp-molecular-profiling-toward-treatment-of-a-rare-malignancy
#4
Elizabeth M Gleeson, Rebecca Feldman, Beth L Mapow, Lynn T Mackovick, Kristine M Ward, William F Morano, Rene R Rubin, Wilbur B Bowne
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization)...
March 3, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#5
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
February 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28257838/als-causing-cleavages-of-tdp-43-abolish-its-rrm2-structure-and-unlock-ctd-for-enhanced-aggregation-and-toxicity
#6
Yuanyuan Wei, Liangzhong Lim, Lu Wang, Jianxing Song
Pathological TDP-43 is cleaved into various fragments. Two major groups of ∼35 and ∼25 kDa have enhanced aggregation and cytotoxicity but the underlying mechanisms remain elusive. While the ∼35-kDa fragments contain entire RRM1, RRM2 and C-terminal domain (CTD) with a middle hydrophobic segment flanked by two prion-like regions; the ∼25-kDa one cleaved at Arg208 only consists of the truncated RRM2 and CTD. Remarkably, the 25-kDa fragment was characterized to induce cell death by gain of cytotoxicity and recapitulate pathological features of TDP-43 proteinopathies...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28196013/prognostic-implications-of-expression-profiling-for-gemcitabine-related-genes-hent1-dck-rrm1-rrm2-in-patients-with-resectable-pancreatic-adenocarcinoma-receiving-adjuvant-chemotherapy
#7
Marek Sierzega, Radosław Pach, Piotr Kulig, Janusz Legutko, Jan Kulig
OBJECTIVES: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). METHODS: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28192940/analysis-of-tertiary-interactions-between-sart3-and-u6-small-nuclear-rna-using-modified-nanocapillaries
#8
Choongman Lee, Joon Kyu Park, Yeoan Youn, Joo Hyoung Kim, Kyo-Seok Lee, Nak-Kyoon Kim, Eunji Kim, Eunice Eunkyeong Kim, Kyung-Hwa Yoo
We employed modified glass nanocapillaries to investigate interactions between the RNA-binding protein, known as cell carcinoma antigen recognized by T cells-3 (SART3), and the noncoding spliceosome component, U6 small nuclear RNA (snRNA), at the single-molecule level. We functionalized the nanocapillaries with U6 snRNA fragments, which were hybridized to DNA molecules and then covalently attached to the nanocapillary surface. When transported through the modified nanocapillaries, two different SART3-derived constructs, HAT-RRM1-RRM2 and RRM1-RRM2, exhibited resistive ionic current pulses with different dwell times, which represented their different binding affinities to tethered U6 snRNAs...
February 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28176818/mechanisms-responsible-for-the-synergistic-antileukemic-interactions-between-atr-inhibition-and-cytarabine-in-acute-myeloid-leukemia-cells
#9
Jun Ma, Xinyu Li, Yongwei Su, Jianyun Zhao, Daniel A Luedtke, Valeria Epshteyn, Holly Edwards, Guan Wang, Zhihong Wang, Roland Chu, Jeffrey W Taub, Hai Lin, Yue Wang, Yubin Ge
Acute myeloid leukemia (AML) continues to be a challenging disease to treat, thus new treatment strategies are needed. In this study, we investigated the antileukemic effects of ATR inhibition alone or combined with cytarabine in AML cells. Treatment with the ATR-selective inhibitor AZ20 caused proliferation inhibition in AML cell lines and primary patient samples. It partially abolished the G2 cell cycle checkpoint and caused DNA replication stress and damage, accompanied by CDK1-independent apoptosis and downregulation of RRM1 and RRM2...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096683/clinicopathological-and-immunohistochemical-features-of-lung-invasive-mucinous-adenocarcinoma-based-on-computed-tomography-findings
#10
Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata
BACKGROUND: We performed an analysis to clarify differences in clinicopathological and molecular features of lung invasive mucinous adenocarcinoma (IMA) based on computed tomography (CT) findings and their impact on prognosis. PATIENTS AND METHODS: On the basis of CT findings, we divided lung IMA into three subtypes: solid, bubbling, and pneumonic. We then investigated differences in clinicopathological characteristics, prognosis, and the expressions of well-identified biomarkers, including cyclooxygenase-2 (Cox-2), excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), class III beta-tubulin, thymidylate synthase (TS), secreted protein acidic and rich in cysteine (SPARC), programmed cell death-1 ligand-1 (PD-L1), and epidermal growth factor receptor mutation, among the three subtypes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28056823/clinical-significance-of-ugt1a1-polymorphism-and-expression-of-ercc1-brca1-tyms-rrm1-tubb3-stmn1-and-top2a-in-gastric-cancer
#11
Yongkuan Cao, Guohu Zhang, Peihong Wang, Jun Zhou, Wei Gan, Yaning Song, Ling Huang, Ya Zhang, Guode Luo, Jiaqing Gong, Lin Zhang
BACKGROUND: Individualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed. METHODS: Ninety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015...
January 5, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28045380/structure-and-conformational-plasticity-of-the-u6-small-nuclear-ribonucleoprotein-core
#12
Eric J Montemayor, Allison L Didychuk, Honghong Liao, Panzhou Hu, David A Brow, Samuel E Butcher
U6 small nuclear RNA (snRNA) is a key component of the active site of the spliceosome, a large ribonucleoprotein complex that catalyzes the splicing of precursor messenger RNA. Prior to its incorporation into the spliceosome, U6 is bound by the protein Prp24, which facilitates unwinding of the U6 internal stem-loop (ISL) so that it can pair with U4 snRNA. A previously reported crystal structure of the `core' of the U6 small nuclear ribonucleoprotein (snRNP) contained an ISL-stabilized A62G mutant of U6 bound to all four RNA-recognition motif (RRM) domains of Prp24 [Montemayor et al...
January 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/27997336/transcriptional-signatures-of-somatic-neoblasts-and-germline-cells-in-macrostomum-lignano
#13
Magda Grudniewska, Stijn Mouton, Daniil Simanov, Frank Beltman, Margriet Grelling, Katrien de Mulder, Wibowo Arindrarto, Philipp M Weissert, Stefan van der Elst, Eugene Berezikov
The regeneration-capable flatworm Macrostomum lignano is a powerful model organism to study the biology of stem cells in vivo. As a flatworm amenable to transgenesis, it complements the historically used planarian flatworm models, such as Schmidtea mediterranea. However, information on the transcriptome and markers of stem cells in M. lignano is limited. We generated a de novo transcriptome assembly and performed the first comprehensive characterization of gene expression in the proliferating cells of M. lignano, represented by somatic stem cells, called neoblasts, and germline cells...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27930710/urb-rip-an-adaptable-and-efficient-approach-for-immunoprecipitation-of-rnas-and-associated-rnas-proteins
#14
Kyle A Cottrell, Sergej Djuranovic
Post-transcriptional regulation of gene expression is an important process that is mediated by interactions between mRNAs and RNA binding proteins (RBP), non-coding RNAs (ncRNA) or ribonucleoproteins (RNP). Key to the study of post-transcriptional regulation of mRNAs and the function of ncRNAs such as long non-coding RNAs (lncRNAs) is an understanding of what factors are interacting with these transcripts. While several techniques exist for the enrichment of a transcript whether it is an mRNA or an ncRNA, many of these techniques are cumbersome or limited in their application...
2016: PloS One
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#15
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
March 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#16
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862552/solution-structure-of-the-first-rna-recognition-motif-domain-of-human-spliceosomal-protein-sf3b49-and-its-mode-of-interaction-with-a-sf3b145-fragment
#17
Kanako Kuwasako, Nobukazu Nameki, Kengo Tsuda, Mari Takahashi, Atsuko Sato, Naoya Tochio, Makoto Inoue, Takaho Terada, Takanori Kigawa, Naohiro Kobayashi, Mikako Shirouzu, Takuhiro Ito, Taiichi Sakamoto, Kaori Wakamatsu, Peter Güntert, Seizo Takahashi, Shigeyuki Yokoyama, Yutaka Muto
The spliceosomal protein SF3b49, a component of the splicing factor 3b (SF3b) protein complex in the U2 small nuclear ribonucleoprotein, contains two RNA recognition motif (RRM) domains. In yeast, the first RRM domain (RRM1) of Hsh49 protein (yeast orthologue of human SF3b49) reportedly interacts with another component, Cus1 protein (orthologue of human SF3b145). Here, we solved the solution structure of the RRM1 of human SF3b49 and examined its mode of interaction with a fragment of human SF3b145 using NMR methods...
February 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27799531/recognition-of-the-3-splice-site-rna-by-the-u2af-heterodimer-involves-a-dynamic-population-shift
#18
Lena Voith von Voithenberg, Carolina Sánchez-Rico, Hyun-Seo Kang, Tobias Madl, Katia Zanier, Anders Barth, Lisa R Warner, Michael Sattler, Don C Lamb
An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27748721/precision-medicine-and-pancreatic-cancer-a-gemcitabine-pathway-approach
#19
James J Farrell, Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine...
November 2016: Pancreas
https://www.readbyqxmd.com/read/27587543/polymorphisms-in-cancer-related-pathway-genes-and-lung-cancer
#20
Shin Yup Lee, Hyo-Gyoung Kang, Jin Eun Choi, Deuk Kju Jung, Won Kee Lee, Hyun Chul Lee, So Yeon Lee, Seung Soo Yoo, Jaehee Lee, Yangki Seok, Eung Bae Lee, Seung Ick Cha, Sukki Cho, Chang Ho Kim, Myung Hoon Lee, Jae Yong Park
We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication...
October 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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