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messenger RNA degradation

George Korza, Emily Camilleri, Joshua Green, Janelle Robinson, Katja Nagler, Ralf Moeller, Melissa J Caimano, Peter Setlow
Large scale shotgun sequencing (RNA-seq) analysis of mRNAs in dormant Bacillus subtilis spores prepared on plates or in liquid generally found the same ∼46 abundant mRNA species, with >250 mRNAs at much lower abundance. Knowledge of the amount of phosphate in a single B. subtilis spore allowed calculation of the amount of mRNA in an individual spore as ∼ 106 nt. Given levels of abundant spore mRNAs compared to those of other mRNAs, it was calculated that the great majority of low abundance mRNAs are present in only small fractions of spores in populations...
February 19, 2019: Journal of Bacteriology
Christopher D Rae, Yuliya Gordiyenko, V Ramakrishnan
During trans-translation, transfer-messenger RNA (tmRNA) and small protein B (SmpB) together rescue ribosomes stalled on a truncated mRNA and tag the nascent polypeptide for degradation. We used cryo-electron microscopy to determine the structures of three key states of the tmRNA-SmpB-ribosome complex during trans translation at resolutions of 3.7 to 4.4 angstroms. The results show how tmRNA and SmpB act specifically on stalled ribosomes and how the circularized complex moves through the ribosome, enabling translation to switch from the old defective message to the reading frame on tmRNA...
February 15, 2019: Science
Linicene Rosa do Nascimento, Caroline Pereira Domingueti
Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD...
February 7, 2019: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Agnès Garcias López, Louise Brogaard, Peter Mh Heegaard, Susanna Cirera, Kerstin Skovgaard
BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNA molecules which regulate gene expression post-transcriptionally and are involved in a multitude of cellular processes. MiRNAs are known to be very stable compared to messenger RNAs (mRNAs), making them excellent candidates as biomarkers for disease. Recently, studies have suggested that miRNA stability in formalin fixed samples might dependend on their nucleotide composition. OBJECTIVE: To explore the stability of a panel of miRNAs isolated from porcine blood and lung tissue after heat and enzyme treatment...
January 30, 2019: MicroRNA
Christophe Rouillon, Januka S Athukoralage, Shirley Graham, Sabine Grüschow, Malcolm F White
Type III CRISPR effector complexes utilize a bound CRISPR RNA (crRNA) to detect the presence of RNA from invading mobile genetic elements in the cell. This RNA binding results in the activation of two enzymatic domains of the Cas10 subunit-the HD nuclease domain, which degrades DNA, and PALM/cyclase domain. The latter synthesizes cyclic oligoadenylate (cOA) molecules by polymerizing ATP, and cOA acts as a second messenger in the cell, switching on the antiviral response by activating host ribonucleases and other proteins...
2019: Methods in Enzymology
Marjorie Gournay, Mathieu Paineau, Jérôme Archambeau, Rémy Pedeux
ING family genes (Inhibitor of Growth) are tumor suppressor genes that play a vital role in cell homeostasis. It has been shown that their expression is lost or diminished in many cancers and other diseases. The main mechanisms by which they are regulated in oncogenesis have not yet been fully elucidated. The involvement of non-coding RNAs (ncRNAs) and in particular microRNAs (miRNAs) in post-transcriptional gene regulation is well established. miRNAs are short sequences (18 to 25 nucleotides) that can bind to the 3 'UTR sequence of the targeted messenger RNA (mRNA), leading to its degradation or translational repression...
January 20, 2019: Cancer Letters
Liya Deng, Jincun Li, Shiyou Lu, Yan Su
The pathogenetic mechanisms of retinoblastoma are still not yet fully elucidated, putting limits to efficacious treatment. Crocin is the main component of saffron, which exhibits significant antitumorigenic properties. The aim of this paper is to investigate the effect of crocin on retinoblastoma. The effects of crocin on the proliferation of human retinoblastoma cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell number assay, and colony formation assay. Cell apoptosis induced by crocin was measured by flow cytometry analysis...
January 23, 2019: Journal of Biochemical and Molecular Toxicology
Qining Yang, Xiaofei Li, Yongwei Zhou, Weicong Fu, Jinhua Wang, Qiang Wei
Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes...
January 22, 2019: Journal of Cellular Biochemistry
Satoshi Uchida, Kazunori Kataoka
Non-viral delivery of plasmid (p)DNA or messenger (m)RNA is a safe and promising therapeutic option to continuously supply therapeutic proteins into diseased tissues. In most cases of in vivo pDNA and mRNA delivery, these nucleic acids are loaded into carriers based on cationic polymers and/or lipids to prevent nuclease-mediated degradation before reaching target cells. The carriers should also evade host clearance mechanisms, including uptake by scavenger cells and filtration in the spleen. Installation of ligands onto the carriers can facilitate their rapid uptake into target cells...
January 21, 2019: Journal of Biomedical Materials Research. Part A
Bohan Rong, Ruonan Feng, Chenlong Liu, Qiong Wu, Chao Sun
Adipocyte-derived exosomes (Exos) serve as bioinformation-containing messengers in cell-to-cell communications, and numerous reports demonstrate that resistin, an adipokine, is strongly associated with hepatic steatosis and other fatty liver diseases, suggesting that adipose dysfunction-generated altered pattern of exosomal cytokines may contribute to shaping the physiological activities in liver. Admittedly, melatonin-mediated positive effects on various tissues/organs have been respectively reported, but regulatory mechanisms of melatonin on the crosstalk between adipose tissue and liver have been investigated rarely...
January 19, 2019: Journal of Pineal Research
Lila E Mullany, Jennifer S Herrick, Lori C Sakoda, Wade Samowitz, John R Stevens, Roger K Wolff, Martha L Slattery
JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of messenger RNAs (mRNAs) and miRNAs using RNA-Seq and Agilent Human miRNA Microarray V19.0 data, respectively, using a negative binomial mixed effects model to test 122 JAK-STAT-signaling genes in 217 colorectal cancer (CRC) cases...
May 2018: Genes & Cancer
Peijun Zhao, Md Badrul Alam, Sang-Han Lee
Ultraviolet B (UVB) irradiation is viewed as the principal inducer of skin photo-aging, associated with acceleration of collagen degradation and upregulation of matrix metalloproteinases (MMPs). The ethnic groups of southern/western China use Fuzhuan brick-tea (FBT) as a beverage and as a nutritional supplement. In this study, we scrutinized the antagonistic effects of aqueous extract of Fuzhuan-brick tea (FBTA) on skin photo-aging in UVB-exposed human keratinocyte (HaCaT) cells. FBTA exhibited strong antioxidant activity and quenched UVB-induced generation of cellular reactive oxygen species (ROS) without showing any toxicity...
December 28, 2018: Nutrients
Joanna Kufel, Pawel Grzechnik
Transcribing RNA Polymerase II interacts with multiple factors that orchestrate maturation and stabilisation of messenger RNA. For the majority of noncoding RNAs, the polymerase complex employs entirely different strategies, which usually direct the nascent transcript to ribonucleolytic degradation. However, some noncoding RNA classes use endo- and exonucleases to achieve functionality. Here we review processing of small nucleolar RNAs that are transcribed by RNA Polymerase II as precursors, and whose 5' and 3' ends undergo processing to release mature, functional molecules...
December 15, 2018: Trends in Genetics: TIG
Julieta Lisa Mateos, Maria José de Leone, Jeanette Torchio, Marlene Reichel, Dorothee Staiger
The circadian clock is an important endogenous timekeeper, helping plants to prepare for the periodic changes of light and darkness in their environment. The clockwork of this molecular timer is made up of clock proteins that regulate transcription of their own genes with a 24 h rhythm. Furthermore, the rhythmically expressed clock proteins regulate time-of-day dependent transcription of downstream genes, causing messenger RNA (mRNA) oscillations of a large part of the transcriptome. On top of the transcriptional regulation by the clock, circadian rhythms in mRNAs rely in large parts on post-transcriptional regulation, including alternative pre-mRNA splicing, mRNA degradation, and translational control...
December 10, 2018: Genes
Agnieszka Tudek, Manfred Schmid, Torben Heick Jensen
In this perspective, we discuss the regulatory impact of nuclear RNA export and decay on messenger RNA (mRNA) functionality. It is well established that control of protein-coding gene expression in eukaryotes employs the regulated production of mRNA, its intra-cellular transfer to cytoplasmic ribosomes and final transcript degradation. Despite a rich body of literature on these events, an involvement of nuclear RNA decay systems remains largely unexplored. Instead, nuclear RNA degradation is often considered a quality control precaution engaged primarily in ridding cells of aberrantly processed transcripts and spurious non-coding RNA...
December 4, 2018: Current Genetics
Anjaneyulu Dirisala, Satoshi Uchida, Theofilus A Tockary, Naoto Yoshinaga, Junjie Li, Shigehito Osawa, Lahari Gorantla, Shigeto Fukushima, Kensuke Osada, Kazunori Kataoka
The major issues in messenger (m)RNA delivery are rapid mRNA degradation in the extracellular and intracellular spaces, which decreases the efficiency and duration for protein expression from mRNA. Stabilization of mRNA carriers using environment-responsive crosslinkings has promises to overcome these issues. Herein, we fine-tuned the structure of disulfide crosslinkings, which are selectively cleaved in the intracellular reductive environment, using the mRNA-loaded polyplex micelles (PMs) prepared from poly(ethylene glycol)-poly(L-lysine) (PEG-PLys) block copolymers, particularly by focusing on cationic charge density after the crosslinking...
November 30, 2018: Journal of Drug Targeting
Charlie Y Mo, Luciano A Marraffini
Athukoralage et al. (2018) identify a new class of nuclease that degrades cyclic oligoadenylate (cOA), a second messenger that activates non-specific RNA degradation by the type III CRISPR-Cas accessory RNase Csm6/Csx1. This discovery provides a mechanism for regulating the degradation of foreign transcripts during the type III CRISPR immune response.
November 15, 2018: Molecular Cell
Filomena de Nigris, Francesco Cacciatore, Francesco P Mancini, Dino F Vitale, Gelsomina Mansueto, Francesco P D'Armiento, Concetta Schiano, Andrea Soricelli, Claudio Napoli
Importance: Although increasingly strong evidence suggests a role of maternal total cholesterol and low-density lipoprotein cholesterol (LDLC) levels during pregnancy as a risk factor for atherosclerotic disease in the offspring, the underlying mechanisms need to be clarified for future clinical applications. Objective: To test whether epigenetic signatures characterize early fetal atherogenesis associated with maternal hypercholesterolemia and to provide a quantitative estimate of the contribution of maternal cholesterol level to fetal lesion size...
November 7, 2018: JAMA Cardiology
Hailing Shi, Xuliang Zhang, Yi-Lan Weng, Zongyang Lu, Yajing Liu, Zhike Lu, Jianan Li, Piliang Hao, Yu Zhang, Feng Zhang, You Wu, Jary Y Delgado, Yijing Su, Meera J Patel, Xiaohua Cao, Bin Shen, Xingxu Huang, Guo-Li Ming, Xiaoxi Zhuang, Hongjun Song, Chuan He, Tao Zhou
N6 -methyladenosine (m6 A), the most prevalent internal RNA modification on mammalian messenger RNAs, regulates the fates and functions of modified transcripts through m6 A-specific binding proteins1-5 . In the nervous system, m6 A is abundant and modulates various neural functions6-11 . Whereas m6 A marks groups of mRNAs for coordinated degradation in various physiological processes12-15 , the relevance of m6 A for mRNA translation in vivo remains largely unknown. Here we show that, through its binding protein YTHDF1, m6 A promotes protein translation of target transcripts in response to neuronal stimuli in the adult mouse hippocampus, thereby facilitating learning and memory...
November 2018: Nature
Ioannis Xinias, Antigoni Mavroudi, Dimitrios Mouselimis, Anastasios Tsarouchas, Konstantina Vasilaki, Ioannis Roilides, Florence Lacaille, Olga Giouleme
Trichohepatoenteric syndrome or syndromic diarrhea is a rare and severe Mendelian autosomal recessive syndrome characterized by intractable diarrhea, facial and hair abnormalities, liver dysfunction, immunodeficiency and failure to thrive. It has been associated with mutations in TTC37 and SKIV2L genes, which encode proteins of the SKI complex that contributes to the cytosolic degradation of the messenger RNA by the cell's exosome. We report a case of a male infant who suffered from typical symptoms and signs of trichohepatoenteric syndrome without immunodeficiency...
2018: SAGE Open Medical Case Reports
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