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Jana Frydlova, Daniel W Rogalsky, Jaroslav Truksa, Lisa Traeger, Andrea U Steinbicker, Martin Vokurka, Jan Krijt
Although the relationship between hereditary hemochromatosis and mutations in the HFE gene was discovered more than 20 years ago, information on the in vivo regulation of HFE protein expression is still limited. The purpose of the study was to determine the response of liver HFE protein content to iron deficiency in mice and rats by immunoblotting. Attempts to visualize the HFE protein in whole liver homogenates were unsuccessful; however, HFE could be detected in liver microsomes or in plasma membrane-enriched fractions...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
N Max Schabla, Greg A Perry, Victoria L Palmer, Patrick C Swanson
The assembly of Ig genes in developing B lymphocytes by V(D)J recombination is initiated by the RAG1-RAG2 endonuclease complex. We previously identified an interaction between RAG1 and viral protein R binding protein (VprBP) (also known as DNA damage binding protein 1 cullin 4-associated factor 1 [DCAF1]), a substrate receptor for the cullin 4-really interesting new gene (RING) E3 ubiquitin ligase (CRL4). We report in this article that in mice, B cell-intrinsic loss of VprBP increases RAG1 protein levels and disrupts expression of the endoribonuclease Dicer, which is essential for microRNA maturation...
June 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Richard B Tunnicliffe, Richard F Collins, Hilda D Ruiz Nivia, Rozanne M Sandri-Goldin, Alexander P Golovanov
The UL69 protein from human cytomegalovirus (HCMV) is a multifunctional regulatory protein and a member of the ICP27 protein family conserved throughout herpesviruses. UL69 plays many roles during productive infection, including the regulation of viral gene expression, nuclear export of intronless viral RNAs, and control of host cell cycle progression. Throughout the ICP27 protein family, an ability to self-associate is correlated with the functions of these proteins in transactivating certain viral genes. Here, we determined the domain boundaries of a globular ICP27 homology domain of UL69, which mediates self-association, and characterized the oligomeric state of the isolated domain...
June 19, 2018: MBio
Anaïs Brosse, Maude Guillier
Small regulatory RNAs are now recognized as key regulators of gene expression in bacteria. They accumulate under specific conditions, most often because their synthesis is directly controlled by transcriptional regulators, including but not limited to alternative sigma factors and response regulators of two-component systems. In turn, small RNAs regulate, mostly at the posttranscriptional level, expression of multiple genes, among which are genes encoding transcriptional regulators. Small RNAs are thus embedded in mixed regulatory circuits combining transcriptional and posttranscriptional controls, and whose properties are discussed here...
May 2018: Microbiology Spectrum
Yiting Wang, Huanbin Wang, Han Yao, Chushu Li, Jing-Yuan Fang, Jie Xu
Immune checkpoint blockade therapies (ICBTs) targeting programmed cell death 1 (PD-1) and its ligand programmed death ligand-1 (PD-L1/B7-H1/CD274) have exhibited momentous clinical benefits and durable responses in multiple tumor types. However, primary resistance is found in considerable number of cancer patients, and most responders eventually develop acquired resistance to ICBT. To tackle these challenges, it is essential to understand how PD-L1 is controlled by cancer cells to evade immune surveillance...
2018: Frontiers in Pharmacology
S Obernikhin, N Yaglova, D Tsomartova, V Torbek, M Ivanova
Chromaffin cells of adrenal medulla have traditionally been considered as modified sympathetic neurons. However, the results of recent studies indicate the need to revise this concept. The article reviews recent findings in origin and ontogeny of adrenal chromaffin cells and transcriptional and posttranscriptional regulation of developmental processes. The article summarizes data on transcriptional control of chromaffin cells proliferation and maturation and participation of microRNA in regulation of chromaffin and sympathetic neuronal phenotype gene expression...
May 2018: Georgian Medical News
Kuan Chai, Xuerao Ning, Thảo Thi Thanh Nguyễn, Boya Zhong, Takao Morinaga, Zhihan Li, Masato Shingyoji, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Naoto Yamaguchi, Masatoshi Tagawa
Heat shock protein 90 (HSP90) inhibitors suppressed MDM4 functions which mediated p53 ubiquitination, and blocked a chaperon function which influenced expression of the client proteins. We examined cytotoxic effects of the inhibitors, 17-allylamino-17-demetheoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), on mesothelioma and investigated combinatory effects of the inhibitors and adenoviruses expressing the wild-type p53 gene (Ad-p53). A majority of mesothelioma lacks p14 and p16 expression, which leads to defective p53 pathway despite bearing the wild-type p53 genotype...
May 25, 2018: Oncotarget
Masashi Fukayama, Akiko Kunita, Atsushi Kaneda
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a representative EBV-infected epithelial neoplasm, which is now included as one of the four subtypes of The Cancer Genome Atlas molecular classification of gastric cancer. In this review, we portray a gastritis-infection-cancer sequence of EBVaGC. This virus-associated type of gastric cancer demonstrates clonal growth of EBV-infected epithelial cells within the mucosa of atrophic gastritis. Its core molecular abnormality is the EBV-specific hyper-epigenotype of CpG island promoter methylation, which induces silencing of tumor suppressor genes...
2018: Advances in Experimental Medicine and Biology
Jieli Pan, Fusheng Jiang, Jia Zhou, Dehong Wu, Zhenhua Sheng, Meiya Li
Lung cancer is one of the leading causes of cancer-related death in the world. MicroRNA- (miR-) 628-3p plays critical roles in many cancers, including lung cancer. We investigated how miR-628-3p affected migration and apoptosis in A549 cells. We used bioinformatics algorithms to predict the miR-628-3p target gene to study the molecular mechanism by which miR-628-3p contributes to lung cancer. Then, we used the luciferase reporter assay to identify whether heat shock protein 90a (HSP90) is a direct target of miR-628-3p...
2018: BioMed Research International
Feiran Wang, Haitao Shi, Shuxiang Wang, Yajing Wang, Zhijun Cao, Shengli Li
Reducing dietary crude protein (CP) and supplementing with certain amino acids (AAs) has been known as a potential solution to improve nitrogen (N) efficiency in dairy production. Thus understanding how AAs are utilized in various sites along the gut is critical. AA flow from the intestine to portal-drained viscera (PDV) and liver then to the mammary gland was elaborated in this article. Recoveries in individual AA in PDV and liver seem to share similar AA pattern with input: output ratio in mammary gland, which subdivides essential AA (EAA) into two groups, lysine (Lys) and branched-chain AA (BCAA) in group 1, input: output ratio > 1; methionine (Met), histidine (His), phenylalanine (Phe) etc...
June 10, 2018: Current Drug Metabolism
Mingjia Chen, Mounashree J Urs, Ismael Sánchez-González, Monilola A Olayioye, Marco Herde, Claus-Peter Witte
N6-methylated adenine (m6A) is the most frequent posttranscriptional modification in eukaryotic mRNA. Turnover of RNA generates N6-methylated AMP (N6-mAMP), which has an unclear metabolic fate. We show that Arabidopsis thaliana and human cells require an N6-mAMP deaminase (ADAL, renamed MAPDA) to catabolize N6-mAMP to inosine monophosphate (IMP) in vivo by hydrolytically removing the aminomethyl group. A phylogenetic, structural, and biochemical analysis revealed that many fungi partially or fully lack MAPDA, which coincides with a minor role of N6A-RNA methylation in these organisms...
June 8, 2018: Plant Cell
Ludger Johannes, Marco Lucchino
RNA interference (RNAi) is a fundamental cellular process for the posttranscriptional regulation of gene expression. RNAi can exogenously be modulated by small RNA oligonucleotides, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), or by antisense oligonucleotides. These small oligonucleotides provided the scientific community with powerful and versatile tools to turn off the expression of genes of interest, and hold out the promise of new therapeutic solutions against a wide range of gene-associated pathologies...
June 2018: Nucleic Acid Therapeutics
Heqin Li, Caili Li, Yuxing Deng, Xuwen Jiang, Shanfa Lu
The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in plants and plays important roles in posttranscriptional regulation. In this study, we combined whole genome sequencing and transcriptomes to systematically investigate PPRs in Salvia miltiorrhiza , which is a well-known material of traditional Chinese medicine and an emerging model system for medicinal plant studies. Among 562 identified SmPPRs , 299 belong to the P subfamily while the others belong to the PLS subfamily. The majority of SmPPRs have only one exon and are localized in the mitochondrion or chloroplast...
June 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yang Hu, Qiong-Ni Zhu, Jun-Li Deng, Zhi-Xing Li, Guo Wang, Yuan-Shan Zhu
Cisplatin (CDDP) is one of the most commonly used chemotherapy drugs for the treatment of various cancers. Although platinum-based therapies are highly efficacious against rapidly proliferating malignant tumors, the development of CDDP resistance results in significant relapse as well as decreased overall survival rates, which is a significant obstacle in CDDP-based cancer therapy. Long non-coding RNAs (lncRNAs) are involved in cancer development and progression by the regulation of processes related to chromatin remodeling, transcription, and posttranscriptional processing...
2018: OncoTargets and Therapy
Davide Roncarati, Vincenzo Scarlato
The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to survive during environmental stresses. The important and widespread human pathogen Helicobacter pylori enrolls a collection of highly conserved heat-shock proteins to preserve cellular proteins and to maintain their homeostasis, allowing the pathogen to adapt and survive in the hostile niche of the human stomach...
June 7, 2018: International Journal of Molecular Sciences
Stephanie Oerum, Martine Roovers, Robert P Rambo, Jola Kopec, Henry J Bailey, Fiona Fitzpatrick, Joseph A Newman, William G Newman, Albert Amberger, Johannes Zschocke, Louis Droogmans, Udo Oppermann, Wyatt W Yue
Mitochondrial tRNAs are transcribed as long polycistronic transcripts of precursor tRNAs and undergo posttranscriptional modifications such as endonucleolytic processing and methylation required for their correct structure and function. Among them, 5'-end processing and purine 9 N1-methylation of mitochondrial tRNA are catalysed by two proteinaceous complexes with overlapping subunit composition. The Mg2+-dependent ribonuclease P complex for 5'-end cleavage comprises the methyltransferase domain-containing protein TRMT10C/MRPP1, short-chain oxidoreductase HSD17B10/MRPP2, and metallonuclease KIAA0391/MRPP3...
June 7, 2018: Journal of Biological Chemistry
Rafaella Nascimento Ferreira, Gustavo Moraes Holanda, Eliana Vieira Pinto Silva, Samir Mansour Moraes Casseb, Karla Fabiane Lopes Melo, Carlos Alberto Marques Carvalho, Juliana Abreu Lima, Pedro Fernando Costa Vasconcelos, Ana Cecília Ribeiro Cruz
Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (Flaviviridae). ZIKV infection is associated with alterations in various organs, including the liver, lungs, and kidneys. Studies on the influence of posttranscriptional control on viral infections have demonstrated that microRNAs (miRNAs) interfere with different stages of the replicative cycle of several viruses and may influence the disease outcome. To shed light on ZIKV-induced regulation of host miRNA-processing machinery in the above organs, we analyzed the expression of genes encoding key proteins of the miRNA pathway in different ZIKV-infected continuous primate cell lineages (HepG2, A549, and MA104) by reverse-transcription quantitative polymerase chain reaction (RT-qPCR)...
June 7, 2018: Viral Immunology
Ayşe Kılıç, Marc Santolini, Taiji Nakano, Matthias Schiller, Mizue Teranishi, Pascal Gellert, Yuliya Ponomareva, Thomas Braun, Shizuka Uchida, Scott T Weiss, Amitabh Sharma, Harald Renz
Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung...
June 7, 2018: JCI Insight
Elias R Gerrick, Thibault Barbier, Michael R Chase, Raylin Xu, Josie François, Vincent H Lin, Matthew J Szucs, Jeremy M Rock, Rushdy Ahmad, Brian Tjaden, Jonathan Livny, Sarah M Fortune
One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated...
June 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jongbo Lee, Minjong Kim, Taichi Q Itoh, Chunghun Lim
Ataxin-2 (ATXN2) is a eukaryotic RNA-binding protein that is conserved from yeast to human. Genetic expansion of a poly-glutamine tract in human ATXN2 has been implicated in several neurodegenerative diseases, likely acting through gain-of-function effects. Emerging evidence, however, suggests that ATXN2 plays more direct roles in neural function via specific molecular and cellular pathways. ATXN2 and its associated protein complex control distinct steps in posttranscriptional gene expression, including poly-A tailing, RNA stabilization, microRNA-dependent gene silencing, and translational activation...
June 5, 2018: Wiley Interdisciplinary Reviews. RNA
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