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messenger RNA degradation

Eun Kyung Choi, Jeong-A Lim, Jong Kwang Kim, Moon Sun Jang, Sun Eui Kim, Hye Jung Baek, Eun Jung Park, Tae Hyun Kim, Chu-Xia Deng, Rui-Hong Wang, Sang Soo Kim
Germline BRCA1 mutations predispose women to breast and ovarian cancer. BRCA1, a large protein with multiple functional domains, interacts with numerous proteins involved in many important biological processes and pathways. However, to date, the role of BRCA1 interactions at specific stages in the progression of mammary tumors, particularly in relation to cell cycle regulation, remains elusive. Here, we demonstrate that BRCA1 interacts with cyclin B1, a crucial cell cycle regulator, and that their interaction is modulated by DNA damage and cell cycle phase...
October 16, 2018: Experimental & Molecular Medicine
Aaron S Mendez, Carolin Vogt, Jens Bohne, Britt A Glaunsinger
A number of viruses remodel the cellular gene expression landscape by globally accelerating messenger RNA (mRNA) degradation. Unlike the mammalian basal mRNA decay enzymes, which largely target mRNA from the 5' and 3' end, viruses instead use endonucleases that cleave their targets internally. This is hypothesized to more rapidly inactivate mRNA while maintaining selective power, potentially though the use of a targeting motif(s). Yet, how mRNA endonuclease specificity is achieved in mammalian cells remains largely unresolved...
October 13, 2018: Nucleic Acids Research
Jeong-Woo Choi, Wenjun Zhou, Zheng-Wen Nie, Ying-Jie Niu, Kyung-Tae Shin, Xiang-Shun Cui
Spindlin 1 (SPIN1), which contains Tudor-like domains, regulates maternal transcripts via interaction with a messenger RNA (mRNA)-binding protein. SPIN1 is involved in tumorigenesis in somatic cells and is highly expressed in cancer cells. Nevertheless, the role of SPIN1 in porcine oocyte maturation remains totally unknown. To explore the function of SPIN1 in porcine oocyte maturation, knockdown, and overexpression techniques were used. SPIN1 mRNA was identified in maternal stages ranging from GV to MII. SPIN1 was localized in the cytoplasm and to chromosomes during meiosis...
October 14, 2018: Journal of Cellular Physiology
Jingjing Wang, Mengmeng Li, Wei Zhang, Aixin Gu, Jiawen Dong, Jianping Li, Anshan Shan
Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production...
October 9, 2018: Toxins
Mohammad A Obeid, Christine Dufès, Sukrut Somani, Alexander B Mullen, Rothwelle J Tate, Valerie A Ferro
RNA interference (RNAi) is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery...
October 8, 2018: Journal of Liposome Research
Kentaro Nakaminami, Motoaki Seki
In addition to plants, all organisms react to environmental stimuli via the perception of signals and subsequently respond through alterations of gene expression. However, genes/mRNAs are usually not the functional unit themselves, and instead, resultant protein products with individual functions result in various acquired phenotypes. In order to fully characterize the adaptive responses of plants to environmental stimuli, it is essential to determine the level of proteins, in addition to the regulation of mRNA expression...
2018: Advances in Experimental Medicine and Biology
Tatsuaki Kurosaki, Keita Miyoshi, Jason R Myers, Lynne E Maquat
Nonsense-mediated messenger RNA decay (NMD) controls mRNA quality and degrades physiologic mRNAs to fine-tune gene expression in changing developmental or environmental milieus. NMD requires that its targets are removed from the translating pool of mRNAs. Since the decay steps of mammalian NMD remain unknown, we developed assays to isolate and sequence direct NMD decay intermediates transcriptome-wide based on their co-immunoprecipitation with phosphorylated UPF1, which is the active form of this essential NMD factor...
October 2018: Nature Structural & Molecular Biology
Fani Memi, Daniela Tirziu, Irinna Papangeli
micro-RNAs (miRNAs) are single-stranded RNA transcripts that bind to messenger RNAs (mRNAs) and inhibit their translation or promote their degradation. To date, miRNAs have been implicated in a large number of biological and disease processes, which has signified the need for the reliable detection methods of miRNA transcripts. Here, we describe a detailed protocol for digoxigenin-labeled (DIG) Locked Nucleic Acid (LNA) probe-based miRNA detection, combined with protein immunostaining on mouse heart sections...
September 15, 2018: Journal of Visualized Experiments: JoVE
Josias B Frazão, Martino Colombo, Cedric Simillion, Adem Bilican, Irene Keller, Daniel Wüthrich, Zhiqing Zhu, Michal J Okoniewski, Rémy Bruggmann, Antonio Condino-Neto, Peter E Newburger
Interferon-γ (IFN-γ) plays an important role in innate and adaptive immunity against intracellular infections and is used clinically for the prevention and control of infections in chronic granulomatous disease (CGD) and inborn defects in the IFN-γ/interleukin (IL)-12 axis. Using transcriptome profiling (RNA-seq), we sought to identify differentially expressed genes, transcripts and exons in Epstein-Barr virus-transformed B lymphocytes (B-EBV) cells from CGD patients, IFN-γ receptor deficiency patients, and normal controls, treated in vitro with IFN-γ for 48 hours...
September 27, 2018: Journal of Cellular Biochemistry
Sheridan M Hoy
Patisiran (ONPATTRO™) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3' untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. Patisiran has been developed by Alnylam Pharmaceuticals; it was recently approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy...
September 24, 2018: Drugs
Mona W Orr, Cordelia A Weiss, Geoffrey B Severin, Husan Turdiev, Soo-Kyoung Kim, Asan Turdiev, Kunquing Liu, Benjamin P Tu, Christopher M Waters, Wade C Winkler, Vincent T Lee
Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that regulates processes such as biofilm formation and virulence. During degradation, c-di-GMP is first linearized to pGpG and subsequently hydrolyzed to two GMPs by a previously unknown enzyme, which was recently identified in Pseudomonas aeruginosa as the 3' to 5' exoribonuclease Oligoribonuclease (Orn). Mutants of orn accumulated pGpG, which inhibited linearization of c-di-GMP. This product inhibition led to elevated c-di-GMP levels, resulting in increased aggregate and biofilm formation...
September 24, 2018: Journal of Bacteriology
Ting Liu, Zhenru Xu, Daming Ou, Jing Liu, Ji Zhang
MicroRNAs (miRNAs) are an important class of endogenous small noncoding single-stranded RNAs that suppress the expression of their target genes through messenger RNA (mRNA) degradation to inhibit transcription and translation. MiRNAs play a crucial regulatory role in many biological processes including proliferation, metabolism, and cellular malignancy. miR-15a/16 is an important tumor suppressor gene cluster with a variety of factors that regulate its transcriptional activity. It has been discovered that a relative reduction of miR-15a/16 expression in various cancers is closely related to the occurrence and progression of tumors...
September 24, 2018: Journal of Cellular Physiology
Peng Sun, Zhen Li, Jingyun Wang, Hui Gao, Xi Yang, Sudong Wu, Deqiang Liu, Qixian Chen
A supramolecular catiomer with a metal-organic framework (MOF) motif was developed to manufacture messenger RNA (mRNA) assemblies. In contrast to the linear catiomer, the dendritic MOF catiomer appeared to markedly improve the colloidal stability of the mRNA assemblies, particularly affording substantial protection to the mRNA payloads from enzymatic degradation, eventually conducing to appreciable mRNA transfection activities at the targeted cells.
October 14, 2018: Chemical Communications: Chem Comm
Nicoletta Machin, Margaret V Ragni
Fitusiran is an RNA interference therapeutic that targets antithrombin (AT) in the liver and interferes with AT translation by binding and degrading messenger RNA-AT, thereby silencing AT gene expression and preventing AT synthesis. In both preclinical and clinical studies, AT knockdown results in dose-dependent AT lowering when fitusiran is given weekly or monthly subcutaneously. In clinical trials, fitusiran dose escalation has resulted in improved thrombin generation and clinical hemostasis as measured by reduction in annualized bleed rate...
2018: Journal of Blood Medicine
Youyou Shao, Lei Chong, Peng Lin, Haiyan Li, Lili Zhu, Qiuping Wu, Changchong Li
Asthma is characterized by chronic inflammation, and long-term chronic inflammation leads to airway remodeling. But the potential regulatory mechanism of airway remodeling is not clearly understood, and there is still no effective way to prevent airway remodeling. Present studies have confirmed the role of microRNAs (miRNAs) in the development of disease, which is known as suppressing translation or degradation of messenger RNA (mRNA) at the posttranscriptional stage. In this study, we described the role of miRNA-133a in asthma and demonstrated it in regulating airway remodeling of asthma through the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway by targeting IGF-1 receptor (IGF1R)...
August 26, 2018: Journal of Cellular Physiology
Yu Xing, Jing Li, Shi-Peng Li, Jiri Xi, Ning Ma, Lei Liu, Jin-Shan Wang, Jin-Zhen Cai
Ischemia-reperfusion (I/R) injury causes cellular dysfunction and a series of immune or apoptotic reactions. Bach1 is a mammalian transcription factor that represses Hmox1, which encodes heme oxygenase-1 (HO-1) that can degrade heme into free iron, carbon monoxide, and biliverdin, to play an important role in antioxidant, anti-inflammatory, and antiapoptotic activities. MicroRNAs (miRNAs) can be found in a variety of eukaryotic cells and viruses, a class of noncoding small RNAs that are encoded by endogenous genes...
August 26, 2018: Journal of Cellular Biochemistry
Jihua Guo, Rong Jia
A lot of evidence has been found on the link between tumorigenesis and the aberrant expression of splicing factors. A number of splicing factors have been reported to be either oncogenic or overexpressed in cancer cells. However, splicing factors can also play negative roles in tumorigenesis. In the current review, we focus on splicing factor poly(rC)-binding protein 1 (PCBP1), a novel tumor suppressor that is characterized by downregulation in many cancer types and shows inhibition of tumor formation and metastasis...
August 21, 2018: Journal of Cellular Physiology
Brenda M Calderon, Graeme L Conn
The 2'-5'-oligoadenylate synthetase (OAS) family of enzymes sense cytosolic dsRNA, a potent signal of viral infection. In response to dsRNA binding, OAS proteins synthesize the second messenger 2'-5'-linked oligoadenylate that activates the latent ribonuclease L (RNase L). RNase L-mediated degradation of viral and cellular RNAs effectively halts viral replication and further stimulates innate immune responses by inducing type I interferon. The OAS/RNase L pathway is therefore central in innate immune recognition and promotion of antiviral host responses...
October 12, 2018: Journal of Biological Chemistry
Jihua Fu, Chen Li, Guangli Zhang, Xin Tong, Haiwei Zhang, Jie Ding, Yingying Ma, Ru Cheng, Shanshan Hou, Shanshan An, Xin Li, Shaoxin Ma
BACKGROUND/AIMS: Previously, we confirmed that liver-synthesized 5-HT rather than non-liver 5-HT, acting on the 5-HT2 receptor (5-HT2R), modulates lipid-induced excessive lipid synthesis (ELS). Here, we further revealed the effects of the hepatocellular 5-HT system in diabetes-related disorders. METHODS: Studies were conducted in male ICR mice, human HepG2 cells, and primary mouse hepatocytes (PMHs) under gene or chemical inhibition of the 5-HT system, key lipid metabolism, and inflammation-related factors...
2018: Cellular Physiology and Biochemistry
Lloyd D Harvey, Stephen Y Chan
Our appreciation of the roles of non-coding RNAs, in particular microRNAs, in the manifestation of pulmonary hypertension (PH) has advanced considerably over the past decade. Comprised of small nucleotide sequences, microRNAs have demonstrated critical and broad regulatory roles in the pathogenesis of PH via the direct binding to messenger RNA transcripts for degradation or inhibition of translation, thereby exerting a profound influence on cellular activity. Yet, as inherently pleiotropic molecules, microRNAs have been difficult to study using traditional, reductionist approaches alone...
August 16, 2018: Journal of Physiology
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