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https://www.readbyqxmd.com/read/27631780/xrn2-autoregulation-and-control-of-polycistronic-gene-expresssion-in-caenorhabditis-elegans
#1
Takashi S Miki, Sarah H Carl, Michael B Stadler, Helge Großhans
XRN2 is a conserved 5'→3' exoribonuclease that complexes with proteins that contain XRN2-binding domains (XTBDs). In Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes XRN2 to retain its activity. XRN2 activity is also promoted by 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1) through hydrolysis of an endogenous XRN inhibitor 3'-phosphoadenosine-5'-phosphate (PAP). Here, we find through unbiased screening that loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion. This unexpected finding is explained by XRN2 autoregulation, which occurs through repression of a cryptic promoter activity and destabilization of the xrn-2 transcript...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27126863/genomes-of-parasitic-nematodes-meloidogyne-hapla-meloidogyne-incognita-ascaris-suum-and-brugia-malayi-have-a-reduced-complement-of-small-rna-interference-pathway-genes-knockdown-can-reduce-host-infectivity-of-m-incognita
#2
Sadia Iqbal, John Fosu-Nyarko, Michael G K Jones
The discovery of RNA interference (RNAi) as an endogenous mechanism of gene regulation in a range of eukaryotes has resulted in its extensive use as a tool for functional genomic studies. It is important to study the mechanisms which underlie this phenomenon in different organisms, and in particular to understand details of the effectors that modulate its effectiveness. The aim of this study was to identify and compare genomic sequences encoding genes involved in the RNAi pathway of four parasitic nematodes: the plant parasites Meloidogyne hapla and Meloidogyne incognita and the animal parasites Ascaris suum and Brugia malayi because full genomic sequences were available-in relation to those of the model nematode Caenorhabditis elegans...
July 2016: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/26843429/rna-cleavage-products-generated-by-antisense-oligonucleotides-and-sirnas-are-processed-by-the-rna-surveillance-machinery
#3
Walt F Lima, Cheryl L De Hoyos, Xue-hai Liang, Stanley T Crooke
DNA-based antisense oligonucleotides (ASOs) elicit cleavage of the targeted RNA by the endoribonuclease RNase H1, whereas siRNAs mediate cleavage through the RNAi pathway. To determine the fates of the cleaved RNA in cells, we lowered the levels of the factors involved in RNA surveillance prior to treating cells with ASOs or siRNA and analyzed cleavage products by RACE. The cytoplasmic 5' to 3' exoribonuclease XRN1 was responsible for the degradation of the downstream cleavage products generated by ASOs or siRNA targeting mRNAs...
April 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/25623408/extended-release-naltrexone-for-alcohol-use-disorders-quasi-experimental-effects-on-mortality-and-subsequent-detoxification-episodes
#4
COMPARATIVE STUDY
Alex H S Harris, Thomas Bowe, Aaron C Del Re, Andrea K Finlay, Elizabeth Oliva, Hugh L Myrick, Anna D Rubinsky
BACKGROUND: Utilization of extended release naltrexone (XRN) for alcohol use disorders (AUDs) in the U.S. Veterans Health Administration (VHA) has been limited, perhaps due to high cost, lack of established superiority over less expensive alternatives including oral naltrexone, and related formulary restrictions. Despite these barriers, pockets of higher utilization exist in VHA, allowing for the quasi-experimental examination of the effects of XRN on 1-year mortality and number of subsequent detoxification episodes among patients with high rates of psychiatric comorbidities and previous psychosocial and pharmacological addiction treatment...
January 2015: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/25110015/regulation-of-mirna-strand-selection-follow-the-leader
#5
REVIEW
Hedda A Meijer, Ewan M Smith, Martin Bushell
miRNA strand selection is the process that determines which of the two strands in a miRNA duplex becomes the active strand that is incorporated into the RISC (RNA-induced silencing complex) (named the guide strand, leading strand or miR) and which one gets degraded (the passenger strand or miR*). Thermodynamic features of the duplex appear to play an important role in this decision; the strand with the weakest binding at its 5'-end is more likely to become the guide strand. Other key characteristics of human miRNA guide strands are a U-bias at the 5'-end and an excess of purines, whereas the passenger strands have a C-bias at the 5'-end and an excess of pyrimidines...
August 2014: Biochemical Society Transactions
https://www.readbyqxmd.com/read/24462208/paxt-1-promotes-xrn2-activity-by-stabilizing-it-through-a-conserved-domain
#6
Takashi S Miki, Hannes Richter, Stefan Rüegger, Helge Großhans
XRN2 is an essential eukaryotic exoribonuclease that processes and degrades various substrates. Here we identify the previously uncharacterized protein R05D11.6/PAXT-1 as a subunit of an XRN2 complex in C. elegans. Targeted paxt-1 inactivation through TALEN-mediated genome editing reduces XRN2 levels, decreases miRNA turnover activity, and results in worm death, which can be averted by overexpressing xrn-2. Hence, stabilization of XRN2 is a major function of PAXT-1. A truncated PAXT-1 protein retaining a predicted domain of unknown function (DUF3469) suffices to restore viability to paxt-1 mutant animals, elevates XRN2 levels, and binds to XRN2...
January 23, 2014: Molecular Cell
https://www.readbyqxmd.com/read/24445807/engineering-of-a-conditional-allele-reveals-multiple-roles-of-xrn2-in-caenorhabditis-elegans-development-and-substrate-specificity-in-microrna-turnover
#7
Takashi S Miki, Stefan Rüegger, Dimos Gaidatzis, Michael B Stadler, Helge Großhans
Although XRN2 proteins are highly conserved eukaryotic 5'→3' exonucleases, little is known about their function in animals. Here, we characterize Caenorhabditis elegans XRN2, which we find to be a broadly and constitutively expressed nuclear protein. An xrn-2 null mutation or loss of XRN2 catalytic activity causes a molting defect and early larval arrest. However, by generating a conditionally mutant xrn-2ts strain de novo through an approach that may be also applicable to other genes of interest, we reveal further functions in fertility, during embryogenesis and during additional larval stages...
April 2014: Nucleic Acids Research
https://www.readbyqxmd.com/read/23974437/ribosome-biogenesis-requires-a-highly-diverged-xrn-family-5-3-exoribonuclease-for-rrna-processing-in-trypanosoma-brucei
#8
Joseph Sakyiama, Sara L Zimmer, Martin Ciganda, Noreen Williams, Laurie K Read
Although biogenesis of ribosomes is a crucial process in all organisms and is thus well conserved, Trypanosoma brucei ribosome biogenesis, of which maturation of rRNAs is an early step, has multiple points of divergence. Our aim was to determine whether in the processing of the pre-rRNA precursor molecule, 5'→3' exoribonuclease activity in addition to endonucleolytic cleavage is necessary in T. brucei as in other organisms. Our approach initiated with the bioinformatic identification of a putative 5'→3' exoribonuclease, XRNE, which is highly diverged from the XRN2/Rat1 enzyme responsible for rRNA processing in other organisms...
October 2013: RNA
https://www.readbyqxmd.com/read/23748567/uridylation-prevents-3-trimming-of-oligoadenylated-mrnas
#9
François Michaël Sement, Emilie Ferrier, Hélène Zuber, Rémy Merret, Malek Alioua, Jean-Marc Deragon, Cécile Bousquet-Antonelli, Heike Lange, Dominique Gagliardi
Degradation of mRNAs is usually initiated by deadenylation, the shortening of long poly(A) tails to oligo(A) tails of 12-15 As. Deadenylation leads to decapping and to subsequent 5' to 3' degradation by XRN proteins, or alternatively 3' to 5' degradation by the exosome. Decapping can also be induced by uridylation as shown for the non-polyadenylated histone mRNAs in humans and for several mRNAs in Schizosaccharomyces pombe and Aspergillus nidulans. Here we report a novel role for uridylation in preventing 3' trimming of oligoadenylated mRNAs in Arabidopsis...
August 2013: Nucleic Acids Research
https://www.readbyqxmd.com/read/23541767/the-decapping-scavenger-enzyme-dcs-1-controls-microrna-levels-in-caenorhabditis-elegans
#10
Gabriel D Bossé, Stefan Rüegger, Maria C Ow, Alejandro Vasquez-Rifo, Evelyne L Rondeau, Victor R Ambros, Helge Grosshans, Martin J Simard
In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA. Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs...
April 25, 2013: Molecular Cell
https://www.readbyqxmd.com/read/23517755/xrn-5-%C3%A2-3-exoribonucleases-structure-mechanisms-and-functions
#11
REVIEW
Vinay K Nagarajan, Christopher I Jones, Sarah F Newbury, Pamela J Green
The XRN family of 5'→3' exoribonucleases is critical for ensuring the fidelity of cellular RNA turnover in eukaryotes. Highly conserved across species, the family is typically represented by one cytoplasmic enzyme (XRN1/PACMAN or XRN4) and one or more nuclear enzymes (XRN2/RAT1 and XRN3). Cytoplasmic and/or nuclear XRNs have proven to be essential in all organisms tested, and deficiencies can have severe developmental phenotypes, demonstrating that XRNs are indispensable in fungi, plants and animals. XRNs degrade diverse RNA substrates during general RNA decay and function in specialized processes integral to RNA metabolism, such as nonsense-mediated decay (NMD), gene silencing, rRNA maturation, and transcription termination...
June 2013: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/22540040/surveillance-of-3-noncoding-transcripts-requires-fiery1-and-xrn3-in-arabidopsis
#12
Yukio Kurihara, Robert J Schmitz, Joseph R Nery, Matthew D Schultz, Emiko Okubo-Kurihara, Taeko Morosawa, Maho Tanaka, Tetsuro Toyoda, Motoaki Seki, Joseph R Ecker
Eukaryotes possess several RNA surveillance mechanisms that prevent undesirable aberrant RNAs from accumulating. Arabidopsis XRN2, XRN3, and XRN4 are three orthologs of the yeast 5'-to-3' exoribonuclease, Rat1/Xrn2, that function in multiple RNA decay pathways. XRN activity is maintained by FIERY1 (FRY1), which converts the XRN inhibitor, adenosine 3', 5'-bisphosphate (PAP), into 5'AMP. To identify the roles of XRNs and FRY1 in suppression of non-coding RNAs, strand-specific genome-wide tiling arrays and deep strand-specific RNA-Seq analyses were carried out in fry1 and xrn single and double mutants...
April 2012: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/22128124/evidence-for-a-sal1-pap-chloroplast-retrograde-pathway-that-functions-in-drought-and-high-light-signaling-in-arabidopsis
#13
Gonzalo M Estavillo, Peter A Crisp, Wannarat Pornsiriwong, Markus Wirtz, Derek Collinge, Chris Carrie, Estelle Giraud, James Whelan, Pascale David, Hélène Javot, Charles Brearley, Rüdiger Hell, Elena Marin, Barry J Pogson
Compartmentation of the eukaryotic cell requires a complex set of subcellular messages, including multiple retrograde signals from the chloroplast and mitochondria to the nucleus, to regulate gene expression. Here, we propose that one such signal is a phosphonucleotide (3'-phosphoadenosine 5'-phosphate [PAP]), which accumulates in Arabidopsis thaliana in response to drought and high light (HL) stress and that the enzyme SAL1 regulates its levels by dephosphorylating PAP to AMP. SAL1 accumulates in chloroplasts and mitochondria but not in the cytosol...
November 2011: Plant Cell
https://www.readbyqxmd.com/read/21755479/micrornases-and-the-regulated-degradation-of-mature-animal-mirnas
#14
Helge Großhans, Saibal Chatterjee
microRNAs (miRNAs) are small noncoding RNAs that regulate numerous target mRNAs through an antisense mechanism. Initially thought to be very stable with half-lives on the orderof days, mature miRNAs haverecently been shown to be subject to degradation by 'microRNases' (miRNases) in plants (the small RNA degrading nucleases, SDN) and animals (exoribonuclease 2/XRN-2/XRN2). Interference with these miRNA turnover pathways causes excess miRNA activity, consistent with an important contribution to miRNA homeostasis...
2011: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/21755478/turnover-of-mature-mirnas-and-sirnas-in-plants-and-algae
#15
Heriberto Cerutti, Fadia Ibrahim
microRNAs (miRNAs) and small interfering RNAs (siRNAs) play important roles in gene regulation and defense responses against transposons and viruses in eukaryotes. These small RNAs generally trigger the silencing of cognate sequences through a variety of mechanisms, including RNA degradation, translational inhibition and transcriptional repression. In the past few years, the synthesis and the mode of action of miRNAs and siRNAs have attracted great attention. However, relatively little is known about mechanisms of quality control during small RNA biogenesis as well as those that regulate mature small RNA stability...
2011: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/21632757/genomic-and-proteomic-analysis-of-invertebrate-iridovirus-type-9
#16
Chun K Wong, Vivienne L Young, Torsten Kleffmann, Vernon K Ward
Iridoviruses (IV) are nuclear cytoplasmic large DNA viruses that are receiving increasing attention as sublethal pathogens of a range of insects. Invertebrate iridovirus type 9 (IIV-9; Wiseana iridovirus) is a member of the major phylogenetic group of iridoviruses for which there is very limited genomic and proteomic information. The genome is 205,791 bp, has a G+C content of 31%, and contains 191 predicted genes, with approximately 20% of its repeat sequences being located predominantly within coding regions...
August 2011: Journal of Virology
https://www.readbyqxmd.com/read/21627036/micrornases-and-the-regulated-degradation-of-mature-animal-mirnas
#17
REVIEW
Helge Grosshans, Saibal Chatterjee
microRNAs (miRNAs) are small noncoding RNAs that regulate numerous target mRNAs through an antisense mechanism. Initially thought to be very stable with half-lives on the order of days, mature miRNAs have recently been shown to be subject to degradation by 'microRNases' (miRNases) in plants (the small RNA degrading nucleases, SDN) and animals (exoribonuclease 2/XRN-2/XRN2). Interference with these miRNA turnover pathways causes excess miRNA activity, consistent with an important contribution to miRNA homeostasis...
2010: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/21627035/turnover-of-mature-mirnas-and-sirnas-in-plants-and-algae
#18
REVIEW
Heriberto Cerutti, Fadia Ibrahim
microRNAs (miRNAs) and small interfering RNAs (siRNAs) play important roles in gene regulation and defense responses against transposons and viruses in eukaryotes. These small RNAs generally trigger the silencing of cognate sequences through a variety of mechanisms, including RNA degradation, translational inhibition and transcriptional repression. In the past few years, the synthesis and the mode of action of miRNAs and siRNAs have attracted great attention. However, relatively little is known about mechanisms of quality control during small RNA biogenesis as well as those that regulate mature small RNA stability...
2010: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/21402112/silencing-of-nbxrn4-facilitates-the-systemic-infection-of-tobacco-mosaic-virus-in-nicotiana-benthamiana
#19
Jiejun Peng, Jian Yang, Fei Yan, Yuwen Lu, Shanshan Jiang, Lin Lin, Hongying Zheng, Hairu Chen, Jianping Chen
The 5'-3' exoribonucleases (Xrns) play key roles in degradation and processing pathways of several classes of RNAs including mRNA, rRNA, miRNA and other small RNAs. Recent work revealed that the cytoplasmic Xrn (Xrn1p in yeast and Xrn4 in plants) affected the stability of the viral RNA of tombusviruses in yeast and plants, which indicates that the cytoplasmic Xrn might be involved in plant defense against virus by degrading viral RNA. Here, we demonstrated that silencing of Nicotiana benthamiana cytoplasmic Xrn4 facilitated both local and systemic infection of Tobacco mosaic virus (TMV) in N...
June 2011: Virus Research
https://www.readbyqxmd.com/read/21397849/target-mediated-protection-of-endogenous-micrornas-in-c-elegans
#20
Saibal Chatterjee, Monika Fasler, Ingo Büssing, Helge Grosshans
MicroRNAs (miRNAs) are tightly regulated through transcriptional and posttranscriptional mechanisms, including degradation by nucleases. Here, we report that in C. elegans, target mRNAs can protect their cognate miRNAs from degradation in vivo. We show that the let-7(n2853) mutation destabilizes the mature let-7 miRNA by impairing this protection. Moreover, presence of a cognate target or depletion of the xrn-1 (XRN1) or xrn-2 (XRN2/Rat1p) exoribonucleases enforces accumulation of certain miRNA passenger (miR(∗)) strands...
March 15, 2011: Developmental Cell
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