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messenger RNA degradation

Feiran Zhang, Yunhee Kang, Mengli Wang, Yujing Li, Tianlei Xu, Wei Yang, Hongjun Song, Hao Wu, Qiang Shu, Peng Jin
N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this reversible RNA modification can be interpreted by cytoplasmic and nuclear "m6A reader" proteins to fine-tune gene expression, such as mRNA degradation and translation initiation. Here we profiled transcriptome-wide m6A sites in adult mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic modification in brain. Interestingly, the mRNA targets of fragile X mental retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A marks...
August 9, 2018: Human Molecular Genetics
Kai Jun Koh, Yi Liu, Seng Han Lim, Xian Jun Loh, Lifeng Kang, Chee Yen Lim, Kyle K L Phua
In this paper, we report a proof of concept study on the fabrication, characterization and therapeutic evaluation of in vitro transcribed messenger RNA (mRNA) loaded in a dissolving microneedle patch (RNApatch). We show that low molecular weight polyvinylpyrrolidone (PVP) can directly be used without further purification for RNApatch fabrication with no detectable mRNA degradation. Physical and functional integrity of mRNA stored within the RNApatch are completely preserved for at least 2 weeks under ambient conditions...
August 7, 2018: Scientific Reports
Fei Liu, Meixiang Sang, Lingjiao Meng, Lina Gu, Shina Liu, Juan Li, Cuizhi Geng
MicroRNAs (miRs) are a small non-coding RNA family with a length of 18-22 nucleotides. They are able to regulate gene expression by either triggering target messenger RNA degradation or by inhibiting mRNA translation. Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3); it is also able to silence a bundle of tumor suppressor genes through promoter binding. However, little is known regarding the effect of miR‑92b on cell autophagy, viability and invasion as well as how it interacts with EZH2...
July 18, 2018: International Journal of Oncology
Katarzyna Gaweda-Walerych, Emilia J Sitek, Ewa Narożańska, Michalina Wezyk, Bogna Brockhuis, Cezary Zekanowski, Jarosław Sławek
Loss-of-function mutations in progranulin (PGRN) gene cause frontotemporal lobar degeneration. Here, we report a case of a 63-year-old woman with a 2-year history of speech impairment, diagnosed with a nonfluent variant of primary progressive aphasia, a subtype of frontotemporal lobar degeneration. In this patient, a novel heterozygous frameshift mutation, c.77delG, in exon 2 of PGRN gene, introducing premature stop codon, p.(C26SfsX28), has been identified. Cultured fibroblasts derived from the patient and her asymptomatic first-degree relative with c...
July 2, 2018: Neurobiology of Aging
Eyal Peer, Sharon Moshitch-Moshkovitz, Gideon Rechavi, Dan Dominissini
The cellular proteome reflects the total outcome of many regulatory mechanisms that affect the metabolism of messenger RNA (mRNA) along its pathway from synthesis to degradation. Accumulating evidence in recent years has uncovered the roles of a growing number of mRNA modifications in every step along this pathway, shaping translational output. mRNA modifications affect the translation machinery directly, by influencing translation initiation, elongation and termination, or by altering mRNA levels and subcellular localization...
July 23, 2018: Cold Spring Harbor Perspectives in Biology
Chiara Angiolilli, Pawel A Kabala, Aleksander M Grabiec, Marzia Rossato, Wi S Lai, Gianluca Fossati, Paolo Mascagni, Christian Steinkühler, Perry J Blackshear, Kris A Reedquist, Dominique L Baeten, Timothy R D J Radstake
BACKGROUND: Histone deacetylase inhibitors (HDACi) suppress cytokine production in immune and stromal cells of patients with rheumatoid arthritis (RA). Here, we investigated the effects of the HDACi givinostat (ITF2357) on the transcriptional and post-transcriptional regulation of inflammatory markers in RA fibroblast-like synoviocytes (FLS). METHODS: The effects of ITF2357 on the expression and messenger RNA (mRNA) stability of IL-1β-inducible genes in FLS were analyzed using array-based qPCR and Luminex...
July 20, 2018: Arthritis Research & Therapy
Joshua Thody, Leighton Folkes, Zahara Medina-Calzada, Ping Xu, Tamas Dalmay, Vincent Moulton
Small RNAs (sRNAs) are short, non-coding RNAs that play critical roles in many important biological pathways. They suppress the translation of messenger RNAs (mRNAs) by directing the RNA-induced silencing complex to their sequence-specific mRNA target(s). In plants, this typically results in mRNA cleavage and subsequent degradation of the mRNA. The resulting mRNA fragments, or degradome, provide evidence for these interactions, and thus degradome analysis has become an important tool for sRNA target prediction...
July 11, 2018: Nucleic Acids Research
Gavin Hanson, Najwa Alhusaini, Nathan Morris, Thomas Sweet, Jeff Coller
Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increase mRNA stability. However, a direct relationship between elongation rate and mRNA stability has not been established across the entire yeast transcriptome...
July 11, 2018: RNA
Sheril June Ankasha, Mohamad Nasir Shafiee, Norhazlina Abdul Wahab, Raja Affendi Raja Ali, Norfilza Mohd Mokhtar
MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA). Its dysregulation plays a vital role in a variety of biological and pathological processes including cancer. A lot of algorithms have been established to predict the target sites of miRNA, but experimentally identifying and validating its target region is still lacking. Guidance in experimental procedures is really needed to find genuine miRNA targets...
January 30, 2018: Oncology Reviews
Dmitry Zubakov, Joanna Chamier-Ciemińska, Iris Kokmeijer, Agnieszka Maciejewska, Pilar Martínez, Ryszard Pawłowski, Cordula Haas, Manfred Kayser
Establishing the cellular or tissue-type origin of human biological traces found at crimes scenes is forensically relevant, as it allows evaluating the crime relevance of such traces and enables reconstructing the sequence of crime events. Messenger RNA and micro RNA markers are useful for forensic tissue identification, but provide challenges for linking RNA-identified cell/tissue types with DNA-identified trace donors, especially in mixed traces. DNA methylation markers overcome this problem, but provide technical challenges due to the DNA treatment required by most analysis methods...
June 28, 2018: Forensic Science International. Genetics
Atsushi Iwama
Ineffective hematopoiesis is one of the hallmarks of myelodysplastic syndrome (MDS). Recently, several signaling pathways responsible for inefficient erythropoiesis in MDS have been uncovered. The p53-S100a8/S100a9-TLR4 pathway is involved in ineffective erythropoiesis in 5q minus (5q-) syndrome. Somatic mutations target multiple components of the messenger RNA (mRNA) splicing machinery including Splicing Factor 3 Subunit b1 (SF3b1) and Serine Arginine Rich Splicing Factor 2 (SRSF2) in patients with MDS. SF3b1 is the most frequently mutated spliceosome component in MDS and is mutated approximately 85% of the time in MDS with ring sideroblasts (MDS-RS)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Cheryl E Hickmann, Diego Castanares-Zapatero, Louise Deldicque, Peter Van den Bergh, Gilles Caty, Annie Robert, Jean Roeseler, Marc Francaux, Pierre-François Laterre
OBJECTIVES: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. DESIGN: Randomized controlled trial. SETTING: Tertiary mixed ICU. PATIENTS: Adult patients admitted for septic shock within the first 72 hours...
June 27, 2018: Critical Care Medicine
John Lalith Charles Richard, Pieter Johan Adam Eichhorn
Prior to the sequencing of the human genome, it was presumed that most of the DNA coded for proteins. However, with the advent of next-generation sequencing, it has now been recognized that most complex eukaryotic genomes are in fact transcribed into noncoding RNAs (ncRNAs), including a family of transcripts referred to as long noncoding RNAs (lncRNAs). LncRNAs have been implicated in many biological processes ranging from housekeeping functions such as transcription to more specialized functions such as dosage compensation or genomic imprinting, among others...
June 1, 2018: SLAS Technology
Yan Bao, Yunting Pu, Xiang Yu, Brian D Gregory, Renu Srivastava, Stephen H Howell, Diane C Bassham
Macroautophagy/autophagy is a conserved process in eukaryotes that contributes to cell survival in response to stress. Previously, we found that endoplasmic reticulum (ER) stress induces autophagy in plants via a pathway dependent upon AT5G24360/IRE1B (INOSITOL REQUIRING 1-1), an ER membrane-anchored factor involved in the splicing of AT1G42990/BZIP60 (basic leucine zipper protein 60) mRNA. IRE1B is a dual protein kinase and ribonuclease, and here we determined the involvement of the protein kinase catalytic domain, nucleotide binding and RNase domains of IRE1B in activating autophagy...
June 25, 2018: Autophagy
Jian Guo, Huiheng Qu, Ting Shan, Yigang Chen, Ye Chen, Jiazeng Xia
The RNA-binding protein tristetraprolin (TTP) binds to adenosine- uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their microenvironment remains undiscovered...
June 25, 2018: Molecules and Cells
Jing Ge, Jiayu Zhu, Bo Xia, Haigang Cao, Ying Peng, Xiao Li, Taiyong Yu, Guiyan Chu, Gongshe Yang, Xine Shi
Myoblast proliferation and terminal differentiation are the key steps of myogenesis. MicroRNAs are a class of small noncoding RNAs that play important roles in gene expression regulation. They negatively regulate gene expression by causing messenger RNA translational repression or target messenger RNA degradation. Here, we found that microRNA-423-5p (miR-423-5p) is highly expressed in both slow and fast muscles. Our gain-of-function study indicated that miR-423-5p actually plays a negative role in regulating myoblast proliferation and differentiation...
June 20, 2018: Journal of Cellular Biochemistry
Takashi Ishii, Hiroshi Hayakawa, Tatsuhiro Igawa, Takeshi Sekiguchi, Mutsuo Sekiguchi
In aerobically growing cells, the guanine base of RNA is oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG), which induces alteration in their gene expression. We previously demonstrated that the human AUF1 protein binds to 8-oxoG in RNA to induce the selective degradation of oxidized messenger RNA. We herein report that the poly(C)-binding protein PCBP1 binds to more severely oxidized RNA to activate apoptosis-related reactions. While AUF1 binds to oligoribonucleotides carrying a single 8-oxoG, PCBP1 does not bind to such oligoribonucleotides but instead binds firmly to oligoribonucleotides in which two 8-oxoG residues are located nearby...
June 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Evangelos D Karousis, Oliver Mühlemann
Nonsense-mediated mRNA decay (NMD) is arguably the best-studied eukaryotic messenger RNA (mRNA) surveillance pathway, yet fundamental questions concerning the molecular mechanism of target RNA selection remain unsolved. Besides degrading defective mRNAs harboring premature termination codons (PTCs), NMD also targets many mRNAs encoding functional full-length proteins. Thus, NMD impacts on a cell's transcriptome and is implicated in a range of biological processes that affect a broad spectrum of cellular homeostasis...
June 11, 2018: Cold Spring Harbor Perspectives in Biology
X Wang, Y Zhang, G Wei, Z Li, D Tian, W Huang
OBJECTIVE: The objective of this study was to investigate the effect of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) during acute antibody-mediated rejection (AMR). METHODS: NTPDase1 overexpression, NTPDase1 knockout, and wild-type nude mice skin graft models were used to induce acute AMR. NTPDase1 expression in B cells, NTPDase1 messenger RNA expression in skin grafts, extracellular adenosine diphosphate (ADP) concentration, B-cell volume and surface antigens expression, average platelet transport rate, and ultrastructure and apoptosis of skin graft cells were investigated...
June 2018: Transplantation Proceedings
Shweta Jain, Kamla Pathak, Ankur Vaidya
RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy...
September 2018: International Journal of Biological Macromolecules
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