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https://www.readbyqxmd.com/read/28339467/a-non-canonical-rna-degradation-pathway-suppresses-rnai-dependent-epimutations-in-the-human-fungal-pathogen-mucor-circinelloides
#1
Silvia Calo, Francisco E Nicolás, Soo Chan Lee, Ana Vila, Maria Cervantes, Santiago Torres-Martinez, Rosa M Ruiz-Vazquez, Maria E Cardenas, Joseph Heitman
Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28339064/extracellular-matrix-metabolism-disorder-induced-by-mechanical-strain-on-human-parametrial-ligament-fibroblasts
#2
Jie Min, Bingshu Li, Cheng Liu, Wenjun Guo, Shasha Hong, Jianming Tang, Li Hong
Pelvic organ prolapse (POP) is a global health problem that may seriously impact the quality of life of the sufferer. The present study aimed to investigate the potential mechanisms underlying alterations in extracellular matrix (ECM) metabolism in the pathogenesis of POP, by investigating the expression of ECM components in human parametrial ligament fibroblasts (hPLFs) subject to various mechanical strain loads. Fibroblasts derived from parametrial ligaments were cultured from patients with POP and without malignant tumors, who underwent vaginal hysterectomy surgery...
March 24, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338072/a-post-weaning-obesogenic-diet-exacerbates-the-detrimental-effects-of-maternal-obesity-on-offspring-insulin-signaling-in-adipose-tissue
#3
Juliana de Almeida Faria, Daniella Duque-Guimarães, Asha A M Carpenter, Elena Loche, Susan E Ozanne
Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insulin signalling proteins, including insulin receptor substrate-1 (IRS-1). The effects of maternal obesity and offspring obesity were, generally, independent and additive...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337299/poly-r-c-binding-protein-pcbp-1-expression-is-regulated-at-the-post-translation-level-in-thyroid-carcinoma
#4
Ming-Peng Zhang, Wei-San Zhang, Jin Tan, Ming-Hui Zhao, Lin-Juan Lian, Jie Cai
Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein that plays a vital role in a wide variety of biological processes. PCBP1 has been shown to function as a tumor suppressor by negatively regulating translation of pro-metastatic proteins in different cancers. Loss of PCBP1 expression or its Akt2-mediated phosphorylation at serine 43 residue has both been indicated to de-repress its regulation of EMT inducer proteins. Our previous work has established that PCBP1 functions as a tumor suppressor in thyroid cancer, where its translation is inhibited by microRNA-490-3p...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337266/long-non-coding-rna-uca1-promotes-cell-progression-by-acting-as-a-competing-endogenous-rna-of-atf2-in-prostate-cancer
#5
Shilong Zhang, Xinxin Dong, Tongyu Ji, Guoxiao Chen, Lei Shan
Prostate cancer (PCa) is a leading cause of cancer-related deaths in elder men. This disease has limited therapeutic options and poor prognosis as the underlying molecular mechanisms are not clearly understood. LncRNA UCA1 functions as an oncogene in many types of cancers. However, the role of UCA1 in PCa remains unclear. In the present study, we showed that UCA1 was significantly up-regulated in PCa cell lines and tissue samples. High UCA1 expression was positively associated with high gleason score, advanced TNM stage and shorter overall survival of PCa patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336556/human-microrna-548p-decreases-hepatic-apolipoprotein-b-secretion-and-lipid-synthesis
#6
Liye Zhou, M Mahmood Hussain
OBJECTIVE: MicroRNAs (miRs) play important regulatory roles in lipid metabolism. Apolipoprotein B (ApoB), as the only essential scaffolding protein in the assembly of very-low-density lipoproteins, is a target to treat hyperlipidemia and atherosclerosis. We aimed to find out miRs that reduce apoB expression. APPROACH AND RESULTS: Bioinformatic analyses predicted that hsa-miR-548p can interact with apoB mRNA. MiR-548p or control miR was transfected in human and mouse liver cells to test its role in regulating apoB secretion and mRNA expression levels...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28333279/inhibition-of-pim1-kinase-attenuates-inflammation-induced-pro-labour-mediators-in-human-fetal-membranes-in-vitro
#7
Ratana Lim, Gillian Barker, Martha Lappas
STUDY QUESTION: Does proviral integration site for Moloney murine leukemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? SUMMARY ANSWER: PIM1 kinase plays a critical role in fetal membranes in regulating pro-inflammatory and pro-labour mediators. WHAT IS KNOWN ALREADY: Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes...
March 9, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28332352/development-of-inhibitors-targeting-hypoxia-inducible-factor-1-and-2-for-cancer-therapy
#8
REVIEW
Tianchi Yu, Bo Tang, Xueying Sun
Hypoxia is frequently observed in solid tumors and also one of the major obstacles for effective cancer therapies. Cancer cells take advantage of their ability to adapt hypoxia to initiate a special transcriptional program that renders them more aggressive biological behaviors. Hypoxia-inducible factors (HIFs) are the key factors that control hypoxia-inducible pathways by regulating the expression of a vast array of genes involved in cancer progression and treatment resistance. HIFs, mainly HIF-1 and -2, have become potential targets for developing novel cancer therapeutics...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28331087/feline-immunodeficiency-virus-evolutionarily-acquires-two-proteins-vif-and-protease-capable-of-antagonizing-feline-apobec3
#9
Rokusuke Yoshikawa, Junko S Takeuchi, Eri Yamada, Yusuke Nakano, Naoko Misawa, Yuichi Kimura, Fengrong Ren, Takayuki Miyazawa, Yoshio Koyanagi, Kei Sato
The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated anti-viral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28329009/the-expression-and-localization-of-rnase-and-rnase-inhibitor-in-blood-cells-and-vascular-endothelial-cells-in-homeostasis-of-the-vascular-system
#10
Ayaka Ohashi, Aya Murata, Yuichiro Cho, Shizuko Ichinose, Yuriko Sakamaki, Miwako Nishio, Osamu Hoshi, Silvia Fischer, Klaus T Preissner, Takatoshi Koyama
RNA may be released from vascular cells including endothelial cells in the event of injury and in vascular disease. Extracellular RNAs have been recognized as novel procoagulant and permeability-increasing factors. Extracellular RNA may function as inflammatory host alarm signals that serve to amplify the defense mechanism, but it may provide important links to thrombus formation. Extracellular RNA is degraded by RNase. We propose that RNase and its inhibitor RNase inhibitor (RI) act as modulators of homeostasis in the vasculature to control the functions of extracellular RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28325876/comprehensive-and-quantitative-mapping-of-rna-protein-interactions-across-a-transcribed-eukaryotic-genome
#11
Richard She, Anupam K Chakravarty, Curtis J Layton, Lauren M Chircus, Johan O L Andreasson, Nandita Damaraju, Peter L McMahon, Jason D Buenrostro, Daniel F Jarosz, William J Greenleaf
RNA-binding proteins (RBPs) control the fate of nearly every transcript in a cell. However, no existing approach for studying these posttranscriptional gene regulators combines transcriptome-wide throughput and biophysical precision. Here, we describe an assay that accomplishes this. Using commonly available hardware, we built a customizable, open-source platform that leverages the inherent throughput of Illumina technology for direct biophysical measurements. We used the platform to quantitatively measure the binding affinity of the prototypical RBP Vts1 for every transcript in the Saccharomyces cerevisiae genome...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325844/the-sole-lsm-complex-in-cyanidioschyzon-merolae-associates-with-pre-mrna-splicing-and-mrna-degradation-factors
#12
Kirsten A Reimer, Martha R Stark, Lisbeth Carolina Aguilar, Sierra R Stark, Robert D Burke, Jack Moore, Richard P Fahlman, Calvin K Yip, Haruko Kuroiwa, Marlene Oeffinger, Stephen D Rader
Proteins of the Sm and Sm-like (LSm) families, referred to collectively as (L)Sm proteins, are found in all three domains of life, and are known to promote a variety of RNA processes such as base-pair formation, unwinding, RNA degradation, and RNA stabilization. In eukaryotes, (L)Sm proteins have been studied, inter alia, for their role in pre-mRNA splicing. In many organisms, the LSm proteins form two distinct complexes, one consisting of LSm1-7 that is involved in mRNA degradation in the cytoplasm, and the other consisting of LSm2-8 that binds spliceosomal U6 snRNA in the nucleus...
March 21, 2017: RNA
https://www.readbyqxmd.com/read/28324013/acute-parathyroid-hormone-injection-increases-c-terminal-but-not-intact-fibroblast-growth-factor-23-levels
#13
V M Knab, B Corbin, O Andrukhova, J M Hum, P Ni, S Rabadi, A Maeda, K E White, R G Erben, H Jüppner, M Christov
The acute effects of PTH on FGF23 in vivo are not well understood. After a single s.c. PTH(1-34) injection (50nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 mRNA and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by 3-5-fold within two hours following PTH injection, which returned to baseline by 4 hours...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323983/autophagic-degradation-of-collagen-1a1-by-cortisol-in-human-amnion-fibroblasts
#14
Yabing Mi, Wangsheng Wang, Chuyue Zhang, Chao Liu, Jiangwen Lu, Wenjiao Li, Rujuan Zuo, Leslie Myatt, Kang Sun
Rupture of fetal membranes can initiate parturition at both term and preterm. Collagen is the crucial factor determining the tensile strength of the membranes. Toward the end of gestation, a feed-forward regeneration of cortisol via 11β-hydroxysteroid dehydrogenase 1 exists in fetal membranes. It remains undetermined whether cortisol contributes to collagen reduction in fetal membranes. Here we have examined whether cortisol accumulation is a causative factor for collagen reduction in human amnion fibroblasts, the major source of collagens in the membranes...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323907/resveratrol-inhibits-androgen-production-of-human-adrenocortical-h295r-cells-by-lowering-cyp17-and-cyp21-expression-and-activities
#15
Nesa Marti, Nadia Bouchoucha, Kay-Sara Sauter, Christa E Flück
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis...
2017: PloS One
https://www.readbyqxmd.com/read/28323884/a-system-for-coordinated-analysis-of-translational-readthrough-and-nonsense-mediated-mrna-decay
#16
Stacey L Baker, J Robert Hogg
The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing premature termination codons, limiting the expression of potentially deleterious truncated proteins. This activity positions the pathway as a regulator of the severity of genetic diseases caused by nonsense mutations. Because many genetic diseases result from nonsense alleles, therapeutics inducing readthrough of premature termination codons and/or inhibition of NMD have been of great interest. Several means of enhancing translational readthrough have been reported to concomitantly inhibit NMD efficiency, but tools for systematic analysis of mammalian NMD inhibition by translational readthrough are lacking...
2017: PloS One
https://www.readbyqxmd.com/read/28323882/mir-181-interacts-with-signaling-adaptor-molecule-denn-madd-and-enhances-tnf-induced-cell-death
#17
Samira Ghorbani, Farideh Talebi, Sedigheh Ghasemi, Ali Jahanbazi Jahan Abad, Mohammed Vojgani, Farshid Noorbakhsh
MicroRNAs are small noncoding RNAs, which regulate the expression of protein coding transcripts through mRNA degradation or translational inhibition. Numerous reports have highlighted the role of miRNAs in regulating cell death pathways including the expression of genes involved in the induction of apoptosis. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine which can send pro-death signals through its receptor TNFR1. Diverse adaptor molecules including DENN/MADD adaptor protein have been shown to modulate TNF-α pro-death signaling via recruitment of MAP kinases to TNFR1 and activation of pro-survival NFκB signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28321652/role-of-plasminogen-activator-inhibitor-1-in-glucocorticoid-induced-muscle-change-in-mice
#18
Yukinori Tamura, Naoyuki Kawao, Takeshi Shimoide, Kiyotaka Okada, Osamu Matsuo, Hiroshi Kaji
We recently revealed that plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is involved in diabetes, osteoporosis and muscle wasting induced by glucocorticoid (GC) treatment in mice. In the present study, we investigated the detailed mechanisms by which GC induces muscle wasting through PAI-1 in vivo and in vitro. PAI-1 deficiency suppressed the mRNA levels of atrogin1 and muscle RING-Finger Protein 1 (MuRF1), ubiquitin ligases leading to muscle degradation, elevated by GC treatment in the gastrocnemius muscle of mice...
March 20, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28318822/genome-wide-analysis-of-rna-polymerase-ii-termination-at-protein-coding-genes
#19
Carlo Baejen, Jessica Andreani, Phillipp Torkler, Sofia Battaglia, Bjoern Schwalb, Michael Lidschreiber, Kerstin C Maier, Andrea Boltendahl, Petra Rus, Stephanie Esslinger, Johannes Söding, Patrick Cramer
At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3'-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3'-transition in budding yeast. We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the "torpedo" exonuclease Rat1 (XRN2 in human)...
March 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28317028/mycobacterial-caseinolytic-protease-gene-regulator-clgr-is-a-substrate-of-caseinolytic-protease
#20
Yoshiyuki Yamada, Thomas Dick
The mycobacterial caseinolytic protease ClpP1P2 is a degradative protease that recently gained interest as a genetically and pharmacologically validated drug target for tuberculosis. The first whole-cell active ClpP1P2 inhibitor, the human proteasome inhibitor bortezomib, is currently undergoing lead optimization to introduce selectivity for the bacterial target. How inhibition of ClpP1P2 translates into whole-cell antimicrobial activity is little understood. Previous work has shown that the caseinolytic protease gene regulator ClgR is an activator of the clpP1P2 genes and also suggested that this transcription factor may be a substrate of the protease...
March 2017: MSphere
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