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RNA biogenesis

Julia K Nussbacher, Gene W Yeo
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated...
March 15, 2018: Molecular Cell
Meng Liu, Shiyang Shen, Di Wen, Mengru Li, Teng Li, Xiaojie Chen, Zhen Gu, Ran Mo
Protein therapeutics hold increasing interest with promise of revolutionizing the cancer treatment by virtue of potent specific activity and reduced adverse effect. Nonetheless, the therapeutic efficacy of anticancer proteins is highly compromised by multiple successive physiological barriers to protein delivery. Concurrent elimination of bulk tumor cells and highly-tumorigenic cancer stem-like cells (CSCs) has been evidenced as a promising strategy to improve cancer therapy. Here we show that a hierarchically-assembled nanocomposite can self-adaptively transform its particulate property in response to endogenous tumor-associated signals to overcome the sequential barriers and achieve enhanced antitumor efficacy by killing CSCs and bulk tumor cells synchronously...
March 16, 2018: Nano Letters
Aruna Vashishta, Lukasz P Slomnicki, Maciej Pietrzak, Scott C Smith, Murali Kolikonda, Shivani P Naik, Rosanna Parlato, Michal Hetman
Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region...
March 15, 2018: Molecular Neurobiology
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Angeliki Chroni, Dimitris Kardassis
The "HDL hypothesis" supporting that an elevation in HDL cholesterol (HDL-C) levels by drugs or by life style changes should be paralleled by a decrease in the risk for Cardiovascular Disease (CVD) has been challenged by recent epidemiological and clinical studies using HDL-raising drugs. HDL components such as proteins, lipids or small RNA molecules, but not cholesterol itself, possess various atheroprotective functions in different cell types and accumulating evidence supports the new hypothesis that HDL functionality is more important than HDL-C levels for CVD risk prediction...
March 12, 2018: Current Medicinal Chemistry
Yuhan Zhang, Weiwei Liu, Ronghong Li, Jiaqi Gu, Ping Wu, Chao Peng, Jinbiao Ma, Ligang Wu, Yang Yu, Ying Huang
The Tudor domain-containing (Tdrd) family proteins play a critical role in transposon silencing in animal gonads by recognizing the symmetrically dimethylated arginine (sDMA) on the (G/A)R motif of the N-terminal of PIWI family proteins via the eTud domains. Papi, also known as "Tdrd2," is involved in Zucchini-mediated PIWI-interacting RNA (piRNA) 3'-end maturation. Intriguingly, a recent study showed that, in papi mutant flies, only Piwi-bound piRNAs increased in length, and not Ago3-bound or Aub-bound piRNAs...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jie Huang, G Patricia Casas Garcia, Matthew A Perugini, Archa Fox, Charles Bond, Mihwa Lee
Members of the Drosophila Behavior Human Splicing (DBHS) protein family are nuclear proteins implicated in many layers of nuclear functions, including RNA biogenesis as well as DNA repair. Definitive of the DBHS protein family, the conserved DBHS domain provides a dimerization platform that is critical for the structural integrity and function of these proteins. The three human DBHS proteins - splicing factor proline- and glutamine-rich (SFPQ), paraspeckle component 1 (PSPC1), and non-POU domain-containing octamer binding protein (NONO) - form either homo- or heterodimers; however, the relative affinity and mechanistic details of preferential heterodimerization are yet to be deciphered...
March 12, 2018: Journal of Biological Chemistry
Attila Németh, Ingrid Grummt
The nucleolus is the largest nuclear sub-compartment in which the early steps of ribosome biogenesis take place. It also plays an essential role in the assembly and function of non-ribosomal ribonucleoprotein (RNP) complexes, controls cell cycle progression and senses environmental stress. The spatial organization and dynamics of nucleolar proteins and RNA is regulated at different structural levels, which finally determine nucleolar architecture. The intimate link between nucleolar structure and function is reflected by transcription-dependent changes in nucleolus-associated chromatin, overall morphological alterations in response to external cues, and the liquid droplet-like behavior of nucleolar compartments...
March 9, 2018: Current Opinion in Cell Biology
Sergey Melnikov, Kasidet Manakongtreecheep, Dieter Söll
Ribosomal proteins are indispensable components of a living cell, and yet their structures are remarkably diverse in different species. Here we use manually curated structural alignments to provide a comprehensive catalog of structural variations in homologous ribosomal proteins from bacteria, archaea, eukaryotes and eukaryotic organelles. By resolving numerous ambiguities and errors of automated structural and sequence alignments, we uncover a whole new class of structural variations, which reside within seemingly conserved segments of ribosomal proteins...
February 24, 2018: Molecular Biology and Evolution
Karen E Hayes, Jamie A Barr, Mingyi Xie, Joan A Steitz, Ivan Martinez
Cellular quiescence (also known as G0 arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27Kip1 . Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating cellular quiescence. Our recent publication demonstrated the existence of an alternative miRNA biogenesis pathway in primary human foreskin fibroblast (HFF) cells during quiescence...
February 5, 2018: Bio-protocol
Frank Curmi, Ruben J Cauchi
Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro , it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function...
March 9, 2018: Biochemical Society Transactions
Alexis H Bennett, Marie-Francoise O'Donohue, Stacey R Gundry, Aye T Chan, Jeffrey Widrick, Isabelle Draper, Anirban Chakraborty, Yi Zhou, Leonard I Zon, Pierre-Emmanuel Gleizes, Alan H Beggs, Vandana A Gupta
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration...
March 2018: PLoS Genetics
Yong-Jie Liu, Shi-Qing Gao, Yi-Miao Tang, Jie Gong, Xiao Zhang, Yong-Bo Wang, Li-Ping Zhang, Ren-Wei Sun, Quan Zhang, Zhao-Bo Chen, Xiang Wang, Cai-Juan Guo, Sheng-Quan Zhang, Feng-Ting Zhang, Jian-Gang Gao, Hui Sun, Wei-Bing Yang, Wei-Wei Wang, Chang-Ping Zhao
Transcriptome analysis was carried out for wheat seedlings and spikes from hybrid Jingmai 8 and both inbred lines to unravel mechanisms underlying heterosis. Heterosis, known as one of the most successful strategies for increasing crop yield, has been widely exploited in plant breeding systems. Despite its great importance, the molecular mechanism underlying heterosis remains elusive. In the present study, RNA sequencing (RNA-seq) was performed on the seedling and spike tissues of the wheat (Triticum aestivum) hybrid Jingmai 8 (JM8) and its homozygous parents to unravel the underlying mechanisms of wheat heterosis...
March 5, 2018: Planta
Enzo Z Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jérémy Boussier, Valérie Gausson, Hervé Blanc, Thomas Vallet, Hyelee Loyd, Laura I Levi, Sophie Lanciano, Chloé Baron, Sarah H Merkling, Louis Lambrechts, Marie Mirouze, Susan Carpenter, Marco Vignuzzi, Maria-Carla Saleh
The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis...
February 27, 2018: Cell Host & Microbe
Z-Y Le, S Dong, R Zhang, X-P Cai, A Gao, R Xiao, H-L Yu
It was reported that high blood cholesterol levels increased the susceptibility to mitochondrial dysfunction. This study hypothesized that the gestational hypercholesterolemia (HC) could induce the mitochondrial dysfunction in term human placenta. The eligible pregnant women were recruited from Xuanwu Hospital in Beijing during their first prenatal visit (before their 10th week of pregnancy). In total, 19 pregnant women whose serum total cholesterol levels were higher than 7.25 mm at third trimester (measured at 36-38 weeks) were selected as gestational HC...
March 4, 2018: Journal of Developmental Origins of Health and Disease
Maria Dafne Cardamone, Bogdan Tanasa, Carly T Cederquist, Jiawen Huang, Kiana Mahdaviani, Wenbo Li, Michael G Rosenfeld, Marc Liesa, Valentina Perissi
As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways in mammals are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a transcriptional activator of nuclear-encoded mitochondrial genes. GPS2-regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of a nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and brown adipose tissue (BAT) from mice...
March 1, 2018: Molecular Cell
P M Clark, N Chitnis, M Shieh, M Kamoun, F B Johnson, D Monos
The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes...
March 1, 2018: Scientific Reports
Natanael Mansilla, Sofia Racca, Diana E Gras, Daniel H Gonzalez, Elina Welchen
Mitochondrial respiration is an energy producing process that involves the coordinated action of several protein complexes embedded in the inner membrane to finally produce ATP. Complex IV or Cytochrome c Oxidase (COX) is the last electron acceptor of the respiratory chain, involved in the reduction of O₂ to H₂O. COX is a multimeric complex formed by multiple structural subunits encoded in two different genomes, prosthetic groups (heme a and heme a ₃), and metallic centers (CuA and CuB ). Tens of accessory proteins are required for mitochondrial RNA processing, synthesis and delivery of prosthetic groups and metallic centers, and for the final assembly of subunits to build a functional complex...
February 27, 2018: International Journal of Molecular Sciences
Alexandra Iulia Irimie, Alina-Andreea Zimta, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Cornelia Braicu, Ioana Berindan-Neagoe
Previously ignored non-coding RNAs (ncRNAs) have become the subject of many studies. However, there is an imbalance in the amount of consideration that ncRNAs are receiving. Some transcripts such as microRNAs (miRNAs) or small interfering RNAs (siRNAs) have gained much attention, but it is necessary to investigate other "pieces of the RNA puzzle". These can offer a more complete view over normal and pathological cell behavior. The other ncRNA species are less studied, either due to their recent discovery, such as stable intronic sequence RNA (sisRNA), YRNA, miRNA-offset RNAs (moRNA), telomerase RNA component (TERC), natural antisense transcript (NAT), transcribed ultraconserved regions (T-UCR), and pseudogene transcript, or because they are still largely seen as non-coding transcripts with no relevance to pathogenesis...
March 1, 2018: Genes
Yao Song, Wei Feng, Guo-Min Shi, Chao Chen, You-Yi Zhang
MicroRNAs (miRNAs) are small noncoding RNAs that control diverse cellular and developmental events through repression of large sets of target mRNAs. miRNAs expressions were mainly regulated at two levels: transcriptional and post-transcriptional. Transcriptional regulation of miRNA-encoding genes produce specific expression patterns of individual miRNA. However, the mechanism of post-transcriptional regulation of miRNAs remains largely unknown. The present study was aimed to clarify whether HuR, an evolutionary conserved AU-rich binding protein, could regulate miRNAs expressions...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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