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Posttranscriptional modification

Tsehai A J Grell, Anthony P Young, Catherine L Drennan, Vahe Bandarian
TYW1 is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the condensation of pyruvate and N-methylguanosine to form the posttranscriptional modification, 4-demethylwyosine, in situ on transfer RNA (tRNA). Two mechanisms have been proposed for this transformation, with one of the possible mechanisms invoking a Schiff base intermediate formed between a conserved lysine residue and pyruvate. Utilizing a combination of mass spectrometry and X-ray crystallography, we have obtained evidence to support the formation of a Schiff base lysine adduct in TYW1...
May 24, 2018: Journal of the American Chemical Society
Xiang Lan, Guangyao Li, Hongming Liu, Hangwei Fu, Ping Chen, Menggang Liu
BACKGROUND: Transmembrane and ubiquitin-like domain-containing 1 protein (Tmub1) negatively regulates liver regeneration. However, whether this regulation involves posttranscriptional modification of Tmub1 expression is unknown. AIM: The aim of the study was to investigate whether microRNA (miR)-27a/b regulates posttranscriptional modification of Tmub1 and cell proliferation during liver regeneration. METHODS: Tmub1 mRNA 3'-untranslated region (UTR) sequences were analyzed using online software...
May 17, 2018: Digestive Diseases and Sciences
Jiankai Wei, Bo Dong
Long noncoding RNAs (lncRNAs) play important roles in diverse developmental and pathological processes through chromatin reprogramming, cis regulation and posttranscriptional modification. They have been extensively studied in both vertebrates and invertebrates. However, the information of lncRNAs in urochordate is still lacking. In this study, we used the RNA-Seq data from three developmental stages (18, 21 and 42 hours post fertilization, hpf) of embryos and larvae in Ciona savignyi to identify candidate lncRNAs and analyze their expression profiles...
May 10, 2018: Marine Genomics
Tho X Pham, Minkyung Bae, Yoojin Lee, Young-Ki Park, Ji-Young Lee
Histone deacetylation is one of the posttranslational modifications of histones by which eukaryotic cells alter gene transcription. Although fatty acids are the best known macronutrients that modulate gene expression in inflammatory pathways, it is unclear whether common fatty acids in diets can regulate the expression of histone deacetylases (HDACs) in macrophages. We determined the effects of fatty acids, including palmitic acid (PA), oleic acid (OA), linoleic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the expression of HDAC isoforms in RAW 264...
March 10, 2018: Journal of Nutritional Biochemistry
Komal P Singh, Christine Miaskowski, Anand A Dhruva, Elena Flowers, Kord M Kober
Research on gene expression (GE) provides insights into the physiology of a cell or group of cells at a given point in time. Studies of changes in GE can be used to identify patients at higher risk for various medical conditions, a higher symptom burden, and/or the adverse consequences associated with various treatments. The aims of this article are as follows: (1) to describe the different types of RNA transcripts, (2) to describe the processes involved in GE (i.e., RNA transcription, epigenetics, and posttranscriptional modifications), (3) to describe common sources of variation in GE, (4) to describe the most common methods used to measure GE, and (5) to discuss factors to consider when choosing tissue for a GE study...
January 1, 2018: Biological Research for Nursing
Nicola Guzzi, Maciej Cieśla, Phuong Cao Thi Ngoc, Stefan Lang, Sonali Arora, Marios Dimitriou, Kristyna Pimková, Mikael N E Sommarin, Roberto Munita, Michal Lubas, Yiting Lim, Kazuki Okuyama, Shamit Soneji, Göran Karlsson, Jenny Hansson, Göran Jönsson, Anders H Lund, Mikael Sigvardsson, Eva Hellström-Lindberg, Andrew C Hsieh, Cristian Bellodi
Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ "writer" PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification...
April 4, 2018: Cell
Marta Fontcuberta-PiSunyer, Sara Cervantes, Eulàlia Miquel, Sergio Mora-Castilla, Louise C Laurent, Angel Raya, Ramon Gomis, Rosa Gasa
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 (H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells...
May 2018: Biochimica et Biophysica Acta
Qing Zhang
RNA editing is a posttranscriptional modification process that alters the sequence of RNA molecules. RNA editing is related to many human diseases. However, the identification of RNA editing sites typically requires matched genomic sequence or multiple related expression data sets. Here we describe the GIREMI tool (genome-independent identification of RNA editing by mutual information; ) that is designed to accurately and sensitively predict adenosine-to-inosine editing from a single RNA-Seq data set...
2018: Methods in Molecular Biology
Alok Kumar, Jai Prakash Jaiswal, Netrapal Sharma, Supriya Gupta, Anil Kumar
Increasing nutritional value of cereals is one of the important research and breeding objectives to overcome malnutrition in developing countries. The synthesis of grain seed proteins during grain filling is controlled by several mechanisms including transcriptional and posttranscriptional modifications. In the current investigation, transcript abundance analysis of three allelic variants of seed storage protein activator ( Spa A, Spa B and Spa D) and NAM - B1 affecting seed nutrient concentration was carried out in two genotypes (UP 2672 and HS 540) of bread wheat differing in grain protein content...
February 2018: 3 Biotech
E C Martin, A T Qureshi, C B Llamas, M E Burow, A G King, O C Lee, V Dasa, M A Freitas, J A Forsberg, E A Elster, T A Davis, J M Gimble
Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood...
February 7, 2018: Adipocyte
Qiansi Chen, Zhendong Tian, Rui Jiang, Xueao Zheng, Conghua Xie, Jun Liu
A family of NDR1/HIN1-like (NHL) genes that shows homology to the nonrace-specific disease resistance (NDR1) and the tobacco (Nicotiana tabacum) harpin-induced (HIN1) genes is reported to be involved in defense. However, little information about NHL genes is available for the potato (Solanum tuberosum). Here, we report that the expression of StPOTHR1, a member of the NHL gene family, is associated with resistance in potato against Phytophthora infestans, and is specifically induced in inoculation sites. Overexpression of StPOTHR1 enhances resistance against P...
February 19, 2018: Biochemical and Biophysical Research Communications
Nathan H Blewett, Richard J Maraia
The conserved nuclear RNA-binding factor known as La protein arose in an ancient eukaryote, phylogenetically associated with another eukaryotic hallmark, synthesis of tRNA by RNA polymerase III (RNAP III). Because 3'-oligo(U) is the sequence-specific signal for transcription termination by RNAP III as well as the high affinity binding site for La, the latter is linked to the intranuclear posttranscriptional processing of eukaryotic precursor-tRNAs. The pre-tRNA processing pathway must accommodate a variety of substrates that are destined for both common steps as well as tRNA-specific events...
April 2018: Biochimica et Biophysica Acta
Daniel E Rothschild, Dylan K McDaniel, Veronica M Ringel-Scaia, Irving C Allen
Immune system activation is essential to thwart the invasion of pathogens and respond appropriately to tissue damage. However, uncontrolled inflammation can result in extensive collateral damage underlying a diverse range of auto-inflammatory, hyper-inflammatory, and neoplastic diseases. The NF-κB signaling pathway lies at the heart of the immune system and functions as a master regulator of gene transcription. Thus, this signaling cascade is heavily targeted by mechanisms designed to attenuate overzealous inflammation and promote resolution...
February 1, 2018: Journal of Leukocyte Biology
Zhen Liu, Jianzhi Zhang
C-to-U RNA editing enzymatically converts the base C to U in RNA molecules and could lead to nonsynonymous changes when occurring in coding regions. Hundreds to thousands of coding sites were recently found to be C-to-U edited or editable in humans, but the biological significance of this phenomenon is elusive. Here, we test the prevailing hypothesis that nonsynonymous editing is beneficial because it provides a means for tissue- or time-specific regulation of protein function that may be hard to accomplish by mutations due to pleiotropy...
April 1, 2017: Molecular Biology and Evolution
Bronwyn A Lucas, Eitan Lavi, Lily Shiue, Hana Cho, Sol Katzman, Keita Miyoshi, Mikiko C Siomi, Liran Carmel, Manuel Ares, Lynne E Maquat
Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kang-Sheng Liu, Tai-Ping Li, Hua Ton, Xiao-Dong Mao, Ya-Jun Chen
OBJECTIVE: Advances in genomics and molecular biology have led to the discovery of a large group of uncharacterized long noncoding RNAs (lncRNAs). Emerging evidence indicated that many lncRNAs function in multiple biological processes and its dysregulation often causes diseases. Recent studies suggested that almost all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression mainly on three levels, including epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling...
January 20, 2018: Chinese Medical Journal
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
Chong Tang, Rachel Klukovich, Hongying Peng, Zhuqing Wang, Tian Yu, Ying Zhang, Huili Zheng, Arne Klungland, Wei Yan
N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ana Crnković, Mirela Čavužić, Vlatka Godinić-Mikulčić, Gregor Anderluh, Ivana Weygand-Đurašević, Ita Gruić-Sovulj
Aminoacyl-tRNA synthetases (aaRSs) decode genetic information by coupling tRNAs with cognate amino acids. In the archaeon Methanothermobacter thermautotrophicus arginyl- and seryl-tRNA synthetase (ArgRS and SerRS, respectively) form a complex which enhances serylation and facilitates tRNASer recycling through its association with the ribosome. Yet, the way by which complex formation participates in Arg-tRNAArg synthesis is still unresolved. Here we utilized pull down and surface plasmon resonance experiments with truncated ArgRS variants to demonstrate that ArgRS uses its N-terminal domain to establish analogous interactions with both SerRS and cognate tRNAArg , providing a rationale for the lack of detectable SerRS•[ArgRS•tRNAArg ] complex...
April 2018: Biochimie
Sheefa Mirza, Kanisha Shah, Shanaya Patel, Nayan Jain, Rakesh Rawal
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and are poised to capture antigen, migrate to draining lymphoid organs, and postmaturation process. Recent evidences have suggested that tumor microenvironment has an effect on DCs by inactivating various components of the immune system responsible for tumor clearance, eventually leading to tumorigenesis. This inactivation is owed to the epigenetic modifications [ie, microRNA (miRNA)] at the posttranscriptional level, thus regulating the differentiation patterns and functional behavior of DCs...
December 12, 2017: Journal of Immunotherapy
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