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https://www.readbyqxmd.com/read/29109067/the-insertion-in-the-double-stranded-rna-binding-domain-of-human-drosha-is-important-for-its-function
#1
Xiaoxiao Zhang, Peng Li, Jian Lin, Haochu Huang, Bin Yin, Yan Zeng
microRNAs (miRNAs) are first transcribed as long, primary transcripts, which are then processed by multiple enzymes and proteins to generate the single-stranded, approximately 22-nucleotide (nt)-long mature miRNAs. A critical step in animal miRNA biogenesis is the cleavage of primary miRNA transcripts (pri-miRNAs) to produce precursor miRNAs (pre-miRNAs) by the enzyme Drosha. How Drosha recognizes its substrates remains incompletely understood. In this study we constructed a series of human Drosha mutants and examined their enzymatic activities and interaction with RNAs...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29084369/bleomycin-can-cleave-an-oncogenic-non-coding-rna
#2
Matthew Disney, Alicia Angelbello
Non-coding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is if non-coding RNAs are targets of medicines. Bleomycin is a natural product that cleaves DNA, however, it is known to cleave RNA in vitro. Herein, an in-depth analysis of the RNA cleavage preferences of bleomycin A5 is presented. Bleomycin A5 prefers to cleave RNAs with stretches of AU base pairs. Based on these preferences and a bioinformatic analysis, the microRNA10b hairpin precursor was identified as a potential substrate for bleomycin A5...
October 30, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29063830/many-si-shrnas-can-kill-cancer-cells-by-targeting-multiple-survival-genes-through-an-off-target-mechanism
#3
William Putzbach, Quan Q Gao, Monal Patel, Stijn van Dongen, Ashley Haluck-Kangas, Aishe A Sarshad, Elizabeth T Bartom, Kwang-Youn A Kim, Denise M Scholtens, Markus Hafner, Jonathan C Zhao, Andrea E Murmann, Marcus E Peter
Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29056292/epigenetics-and-gene-expression-profile-in-first-episode-psychosis-the-role-of-childhood-trauma
#4
REVIEW
Simona Tomassi, Sarah Tosato
Childhood Trauma (CT) mediation of the epigenome and its impact on gene expression profile could provide a mechanism for the gene-environment interaction underling psychosis. We reviewed the evidence concerning epigenetic and gene expression modifications associated with CT in both First-Episode Psychosis (FEP) and healthy subjects. In order to explore the relative role of psychosis itself in determining these modifications, evidence about FEP and epigenetics/gene expression was also summarized. We performed a systematic search on PubMed, last updated in December 2016...
October 19, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29053842/differential-expression-of-water-channel-and-noncoding-rna-biogenesis-related-genes-in-three-lines-of-chickens-under-a-short-term-water-restriction
#5
S Orlowski, J Flees, N Anthony, S Dridi
Genetic selection for high growth rate has resulted in tremendous changes not only in feed efficiency, but also in water consumption between modern broilers and their ancestor jungle fowl (JF). However molecular mechanisms involved in water homeostasis are still not well defined. This study aimed, therefore, to determine the effect of short-term water restriction on the expression of water channel- and noncoding RNA biogenesis-related genes in the kidney and whole blood of JF, broiler population from the 1990s (RB1995), and modern broiler population developed in 2015 (ARB2015)...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29042235/splicing-factors-as-regulators-of-mirna-biogenesis-links-to-human-disease
#6
REVIEW
Madara Ratnadiwakara, Monika Mohenska, Minna-Liisa Änkö
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally by fine-tuning mRNA levels and translation during development and in adult tissues. miRNAs are transcribed as parts of longer precursors that undergo multiple processing steps before the mature miRNAs reach their target mRNAs in the cytoplasm. In addition to Drosha/DGCR8 and Dicer that are the essential components of the miRNA processing pathway, a range of other RNA binding proteins have recently been implicated in miRNA biogenesis...
October 19, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29036314/mirnovo-genome-free-prediction-of-micrornas-from-small-rna-sequencing-data-and-single-cells-using-decision-forests
#7
Dimitrios M Vitsios, Elissavet Kentepozidou, Leonor Quintais, Elia Benito-Gutiérrez, Stijn van Dongen, Matthew P Davis, Anton J Enright
The discovery of microRNAs (miRNAs) remains an important problem, particularly given the growth of high-throughput sequencing, cell sorting and single cell biology. While a large number of miRNAs have already been annotated, there may well be large numbers of miRNAs that are expressed in very particular cell types and remain elusive. Sequencing allows us to quickly and accurately identify the expression of known miRNAs from small RNA-Seq data. The biogenesis of miRNAs leads to very specific characteristics observed in their sequences...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29020972/sumo1-modification-of-khsrp-regulates-tumorigenesis-by-preventing-the-tl-g-rich-mirna-biogenesis
#8
Haihua Yuan, Rong Deng, Xian Zhao, Ran Chen, Guofang Hou, Hailong Zhang, Yanli Wang, Ming Xu, Bin Jiang, Jianxiu Yu
BACKGROUND: MicroRNAs (miRNAs) are important regulators involved in diverse physiological and pathological processes including cancer. SUMO (small ubiquitin-like modifier) is a reversible protein modifier. We recently found that SUMOylation of TARBP2 and DGCR8 is involved in the regulation of the miRNA pathway. KHSRP is a single stranded nucleic acid binding protein with roles in transcription and mRNA decay, and it is also a component of the Drosha-DGCR8 complex promoting the miRNA biogenesis...
October 11, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28986522/mammalian-ape1-controls-mirna-processing-and-its-interactome-is-linked-to-cancer-rna-metabolism
#9
Giulia Antoniali, Fabrizio Serra, Lisa Lirussi, Mikiei Tanaka, Chiara D'Ambrosio, Shiheng Zhang, Slobodanka Radovic, Emiliano Dalla, Yari Ciani, Andrea Scaloni, Mengxia Li, Silvano Piazza, Gianluca Tell
Mammalian apurinic/apyrimidinic endonuclease 1 is a DNA repair enzyme involved in genome stability and expression of genes involved in oxidative stress responses, tumor progression and chemoresistance. However, the molecular mechanisms underlying the role of apurinic/apyrimidinic endonuclease 1 in these processes are still unclear. Recent findings point to a novel role of apurinic/apyrimidinic endonuclease 1 in RNA metabolism. Through the characterization of the interactomes of apurinic/apyrimidinic endonuclease 1 with RNA and other proteins, we demonstrate here a role for apurinic/apyrimidinic endonuclease 1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28960389/the-other-face-of-an-editor-adar1-functions-in-editing-independent-ways
#10
REVIEW
Konstantin Licht, Michael F Jantsch
The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation...
September 28, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28954229/microprocessor-recruitment-to-elongating-rna-polymerase-ii-is-required-for-differential-expression-of-micrornas
#11
Victoria A Church, Sigal Pressman, Mamiko Isaji, Mary Truscott, Nihal Terzi Cizmecioglu, Stephen Buratowski, Maxim V Frolov, Richard W Carthew
The cellular abundance of mature microRNAs (miRNAs) is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs) into pre-miRNA intermediates. The Microprocessor complex of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor's differential processing of various pri-miRNAs. Here, we show that Drosophila DGCR8 (Pasha) directly associates with the C-terminal domain of the RNA polymerase II elongation complex when it is phosphorylated by the Cdk9 kinase (pTEFb)...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28950226/the-epstein-barr-virus-mir-bhrf1-micrornas-regulate-viral-gene-expression-in-cis
#12
Brigid Chiyoko Poling, Alexander M Price, Micah A Luftig, Bryan R Cullen
The Epstein-Barr virus (EBV) miR-BHRF1 microRNA (miRNA) cluster has been shown to facilitate B-cell transformation and promote the rapid growth of the resultant lymphoblastoid cell lines (LCLs). However, we find that expression of physiological levels of the miR-BHRF1 miRNAs in LCLs transformed with a miR-BHRF1 null mutant (∆123) fails to increase their growth rate. We demonstrate that the pri-miR-BHRF1-2 and 1-3 stem-loops are present in the 3'UTR of transcripts encoding EBNA-LP and that excision of pre-miR-BHRF1-2 and 1-3 by Drosha destabilizes these mRNAs and reduces expression of the encoded protein...
December 2017: Virology
https://www.readbyqxmd.com/read/28943952/mirna-biogenesis-associated-rnase-iii-nucleases-drosha-and-dicer-are-upregulated-in-colorectal-adenocarcinoma
#13
Shin Kim, Mei Ling Song, Hyeonji Min, Ilseon Hwang, Seong Kyu Baek, Taeg Kyu Kwon, Jong-Wook Park
Drosha and Dicer are important regulators of microRNA (miRNA) biogenesis, and it has been suggested that their aberrant regulation may cause colorectal cancer (CRC). The aim of the present study was to evaluate the mRNA expression levels of these two important RNase III nucleases and their association with clinical features in CRC specimens from South Korean patients. The expression levels of Drosha and Dicer mRNA were investigated in 77 CRC tissues and adjacent histologically non-neoplastic tissues using the quantitative polymerase chain reaction...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28934508/a-novel-requirement-for-drosha-in-maintenance-of-mammalian-cg-methylation
#14
Athanasia Stathopoulou, Jyoti B Chhetri, John C Ambrose, Pierre-Olivier Estève, Lexiang Ji, Hediye Erdjument-Bromage, Guoqiang Zhang, Thomas A Neubert, Sriharsa Pradhan, Javier Herrero, Robert J Schmitz, Steen K T Ooi
No abstract text is available yet for this article.
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934503/a-novel-requirement-for-drosha-in-maintenance-of-mammalian-cg-methylation
#15
Athanasia Stathopoulou, Jyoti B Chhetri, John C Ambrose, Pierre-Olivier Estève, Lexiang Ji, Hediye Erdjument-Bromage, Guoqiang Zhang, Thomas A Neubert, Sriharsa Pradhan, Javier Herrero, Robert J Schmitz, Steen K T Ooi
In mammals, faithful inheritance of genomic methylation patterns ensures proper gene regulation and cell behaviour, impacting normal development and fertility. Following establishment, genomic methylation patterns are transmitted through S-phase by the maintenance methyltransferase Dnmt1. Using a protein interaction screen, we identify Microprocessor component DROSHA as a novel DNMT1-interactor. Drosha-deficient embryonic stem (ES) cells display genomic hypomethylation that is not accounted for by changes in the levels of DNMT proteins...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934477/a-structural-map-of-oncomir-1-at-single-nucleotide-resolution
#16
Saikat Chakraborty, Yamuna Krishnan
The miR-17-92a cluster, also known as 'oncomiR-1', is an RNA transcript that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. Its dysregulation underlies the development of several cancers. Oncomir-1 comprises six constituent miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. The structural mechanisms that regulate such differential processing are unknown, and this has impeded our understanding of the dysregulation of oncomiR-1 in pathophysiology...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28884294/a-concise-review-of-microrna-exploring-the-insights-of-microrna-regulations-in-bacterial-viral-and-metabolic-diseases
#17
REVIEW
Ahsan Naveed, Sajjad Ur-Rahman, Sabahat Abdullah, Muhammad Ammar Naveed
MicroRNA (miRNA) is a small section of ribonucleic acid (RNA) that reduces the protein formation by making the pair of the complementary piece of mRNA. The genes of miRNA are present as transcriptional or polycistronic units in the chromosomes. The cellular multiplication, separation and existence like the multitude of genetic functions are affected by miRNA. Nearly 50% of identified miRNA are located in the residence in the intronic part of the genes. The mature miRNA is yielded in two steps. Drosha and RNA-induced silencing complex are the catalysts that play an important role in miRNA synthesis...
December 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28877962/toward-the-human-cellular-micrornaome
#18
Matthew N McCall, Min-Sik Kim, Mohammed Adil, Arun H Patil, Yin Lu, Christopher J Mitchell, Pamela Leal-Rojas, Jinchong Xu, Manoj Kumar, Valina L Dawson, Ted M Dawson, Alexander S Baras, Avi Z Rosenberg, Dan E Arking, Kathleen H Burns, Akhilesh Pandey, Marc K Halushka
MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues...
October 2017: Genome Research
https://www.readbyqxmd.com/read/28866430/the-role-of-microrna-molecules-and-microrna-regulating-machinery-in-the-pathogenesis-and-progression-of-epithelial-ovarian-cancer
#19
REVIEW
Xiyin Wang, Mircea Ivan, Shannon M Hawkins
MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer...
November 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28846091/neat1-scaffolds-rna-binding-proteins-and-the-microprocessor-to-globally-enhance-pri-mirna-processing
#20
Li Jiang, Changwei Shao, Qi-Jia Wu, Geng Chen, Jie Zhou, Bo Yang, Hairi Li, Lan-Tao Gou, Yi Zhang, Yangming Wang, Gene W Yeo, Yu Zhou, Xiang-Dong Fu
MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha-DGCR8 Microprocessor. NONO and PSF are key components of paraspeckles organized by the long noncoding RNA (lncRNA) NEAT1. We further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing...
October 2017: Nature Structural & Molecular Biology
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