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Posttranscriptional modification

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...
March 9, 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...
January 30, 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...
January 31, 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...
January 27, 2018: 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 16, 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 (aaRS) 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...
December 19, 2017: 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
Zhen Liu, Jianzhi Zhang
Methylation of the adenosine base at the nitrogen-6 position (m6A) is the most prevalent internal posttranscriptional modification of mRNAs in many eukaryotes. Despite the rapid progress in the transcriptome-wide mapping of m6As, identification of proteins responsible for writing, reading, and erasing m6As, and elucidation of m6A functions in splicing, RNA stability, translation, and other processes, it is unknown whether most observed m6A modifications are functional. To address this question, we respectively analyze the evolutionary conservation of yeast and human m6As in protein-coding regions...
December 8, 2017: Molecular Biology and Evolution
Yifan Zou, Jianfa Li, Yincong Chen, Huizhong Xiao, Fuyou Zhang, Dan Yu, Kewang Luo
Long non-coding RNAs account for large proportion of non-coding transcripts in human genomes. Though they lack of open reading framework and cannot encode protein, they can control endogenous gene expression though regulating cell life activities. They serve as transcriptional modulator, posttranscriptional processor, chromatin remodeler and splicing regulator during the process of gene modification. Moreover, long non-coding RNAs were regarded as potential tumor markers for cancer diagnosis and prognosis. BANCR was identified as a cancer-promoting long non-coding RNA in melanoma tissues...
November 7, 2017: Oncotarget
Sylwia Bartoszewska, Wojciech Kamysz, Bogdan Jakiela, Marek Sanak, Jarosław Króliczewski, Zsuzsa Bebok, Rafal Bartoszewski, James F Collawn
Background: Hypoxic conditions induce the expression of hypoxia-inducible factors (HIFs) that allow cells to adapt to the changing conditions and alter the expression of a number of genes including the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial cells even during normoxic conditions, but during hypoxia its mRNA expression decreases even further. Methods: In the current studies, we examined the kinetics of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial epithelial cells...
2017: Cellular & Molecular Biology Letters
Daniel C Cole, Youngcheul Chung, Khatuna Gagnidze, Kaitlyn H Hajdarovic, Violeta Rayon-Estrada, Dewi Harjanto, Benedetta Bigio, Judit Gal-Toth, Teresa A Milner, Bruce S McEwen, F Nina Papavasiliou, Karen Bulloch
Microglia (MG), a heterogeneous population of phagocytic cells, play important roles in central nervous system (CNS) homeostasis and neural plasticity. Under steady-state conditions, MG maintain homeostasis by producing antiinflammatory cytokines and neurotrophic factors, support myelin production, and remove synapses and cellular debris, as well as participating in "cross-correction," a process that supplies neurons with key factors for executing autophagy-lysosomal function. As sentinels for the immune system, MG also detect "danger" signals (pathogenic or traumatic insult), become activated, produce proinflammatory cytokines, and recruit monocytes and dendritic cells to the site of damage through a breached blood-brain barrier or via brain lymphatics...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
Violeta Rayon-Estrada, Dewi Harjanto, Claire E Hamilton, Yamina A Berchiche, Emily Conn Gantman, Thomas P Sakmar, Karen Bulloch, Khatuna Gagnidze, Sheila Harroch, Bruce S McEwen, F Nina Papavasiliou
Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
Xing Chen, Ya-Zhou Sun, Hui Liu, Lin Zhang, Jian-Qiang Li, Jia Meng
Ribonucleic acid (RNA) methylation is a type of posttranscriptional modifications occurring in all kingdoms of life. It is strongly related to important biological process, thus making it linked to a number of human diseases. Owing to the development of high-throughput sequencing technology, plenty of achievement had been obtained in RNA methylation research recently. Meanwhile, various computational models have been developed to analyze and mining increasing RNA methylation data. In this review, we first made a brief introduction about eight types of most popular RNA methylation, the biological functions of RNA methylation, the relationship between RNA methylation and disease and five important RNA methylation-related diseases...
November 18, 2017: Briefings in Bioinformatics
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