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RNA Biology

Martin Hart, Fabian Kern, Christina Backes, Stefanie Rheinheimer, Tobias Fehlmann, Andreas Keller, Eckart Meese
MiRNAs play a central role in physiological and pathological processes. Both for the biological understanding and for their clinical application, it is essential to understand the interaction of miRNAs and their targets. Target identification largely hinges on in-silico prediction, which requires a complete consideration of miRNA binding sites within the UTRs of target genes. Here, we show that 5-mer sites might also play an essential role for human miRNA-target binding. We implemented and employed an algorithm to all pairs of 2,588 human miRNAs annotated in miRBase and the 3' UTRs of 16725 genes (>43 million combinations)...
May 11, 2018: RNA Biology
Berta Pozzi, Pablo Mammi, Laureano Bragado, Luciana E Giono, Anabella Srebrow
Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a pre-mRNA substrate during a splicing reaction. We demonstrated that SUMOylation of Prp3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and/or recruitment to active spliceosomes. Expanding upon our previous results, we have shown that the splicing factor SRSF1 stimulates SUMO conjugation to several spliceosomal proteins...
May 9, 2018: RNA Biology
Charith Raj Adkar-Purushothama, Jean-Pierre Perreault
Understanding in intimate details how the viroid interaction with host's defense genes is a cornerstone for developing viroid resistant plants. In this present study, small RNAs (sRNA) derived from Potato spindle tuber viroid (PSTVd) were studied in silico in order to detect any interactions with the serine threonine kinase receptor, a transmembrane protein that plays a role in disease resistance in plants. Using molecular biology techniques, it was determined that PSTVd infection negatively affects at least three serine threonine kinase receptors as well as with three other genes that are known to be involved in the overall development of the tomato plants...
April 23, 2018: RNA Biology
Fabian Amman, Alexandre D'Halluin, Rudy Antoine, Ludovic Huot, Ilona Bibova, Kristina Keidel, Stéphanie Slupek, Peggy Bouquet, Loïc Coutte, Ségolène Caboche, Camille Locht, Branislav Vecerek, David Hot
Bordetella pertussis is the causative agent of whooping cough, a respiratory disease still considered as a major public health threat and for which recent re-emergence has been observed. Constant reshuffling of Bordetella pertussis genome organization was observed during evolution. These rearrangements are essentially mediated by Insertion Sequences (IS), a mobile genetic elements present in more than 230 copies in the genome, which are supposed to be one of the driving forces enabling the pathogen to escape from vaccine-induced immunity...
April 23, 2018: RNA Biology
Adrián E Cambindo Botto, Juan C Muñoz, Manuel J Muñoz
Gene expression and DNA repair are fundamental processes for life. During the last decade, accumulating experimental evidence point towards different modes of coupling between these processes. Here we discuss the molecular mechanisms by which RNAPII-dependent transcription affects repair by the Nucleotide Excision Repair system (NER) and how NER activity, through the generation of single stranded DNA intermediates and activation of the DNA damage response kinase ATR, drives gene expression in a genotoxic scenario...
April 23, 2018: RNA Biology
Katherine I Zhou, Wesley C Clark, David W Pan, Matthew J Eckwahl, Qing Dai, Tao Pan
The abundant RNA modification pseudouridine (Ψ) has been mapped transcriptome-wide by chemically modifying pseudouridines with carbodiimide and detecting the resulting reverse transcription stops in high-throughput sequencing. However, these methods have limited sensitivity and specificity, in part due to the use of reverse transcription stops. We sought to use mutations rather than just stops in sequencing data to identify pseudouridine sites. Here, we identify reverse transcription conditions that allow read-through of carbodiimide-modified pseudouridine (CMC-Ψ), and we show that pseudouridines in carbodiimide-treated human ribosomal RNA have context-dependent mutation and stop rates in high-throughput sequencing libraries prepared under these conditions...
April 23, 2018: RNA Biology
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
Michael Jantsch, Alessandro Quattrone, Mary O'Connell, Mark Helm, Michaela Frye, Manuel Macias-Gonzales, Marie Ohman, Stefan Ameres, Luc Willems, Francois Fuks, Anastasis Oulas, Stepanka Vanacova, Henrik Nielsen, Cecile Bousquet-Antonelli, Yuri Motorin, Jean-Yves Roignant, Nikolaos Balatsos, Andras Dinnyes, Pavel Baranov, Vincent Kelly, Ayelet Lamm, Gideon Rechavi, Mattia Pelizzola, Janis Liepins, Irina Holodnuka Kholodnyuk, Vanessa Zammit, Duncan Ayers, Finn Drablos, John Arne Dahl, Janusz Bujnicki, Carmen Jeronimo, Raquel Almeida, Monica Neagu, Marieta Costache, Jasna Bankovic, Bojana Banovic, Jan Kyselovic, Luis Miguel Valor, Stefan Selbert, Pinar Pir, Turan Demircan, Victoria Cowling, Matthias Schäfer, Walter Rossmanith, Denis Lafontaine, Alexandre David, Clement Carre, Frank Lyko, Raffael Schaffrath, Schraga Schwartz, Andre Verdel, Arne Klungland, Elzbieta Purta, Gordana Timotijevic, Fernando Cardona, Alberto Davalos, Ester Ballana, Donal O Carroll, Jernej Ule, Rupert Fray
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research...
April 19, 2018: RNA Biology
Laura Avogaro, Emmanuelle Querido, Myriam Dalachi, Michael F Jantsch, Pascal Chartrand, Emilio Cusanelli
Telomeres cap the ends of eukaryotic chromosomes, protecting them from degradation and erroneous recombination events which may lead to genome instability. Telomeres are transcribed giving rise to telomeric repeat-containing RNAs, called TERRA. The TERRA long noncoding RNAs have been proposed to play important roles in telomere biology, including heterochromatin formation and telomere length homeostasis. While TERRA RNAs are predominantly nuclear and localize at telomeres, little is known about the dynamics and function of TERRA molecules expressed from individual telomeres...
April 16, 2018: RNA Biology
Lisa-Katharina Maier, Aris-Edda Stachler, Jutta Brendel, Britta Stoll, Susan Fischer, Karina Haas, Thandi Schwarz, Omer S Alkhnbashi, Kundan Sharma, Henning Urlaub, Rolf Backofen, Uri Gophna, Anita Marchfelder
Invading genetic elements pose a constant threat to prokaryotic survival, requiring an effective defence. Eleven years ago, the arsenal of known defence mechanisms was expanded by the discovery of the CRISPR-Cas system. Although CRISPR-Cas is present in the majority of archaea, research often focuses on bacterial models. Here, we provide a perspective based on insights gained studying CRISPR-Cas system I-B of the archaeon Haloferax volcanii. The system relies on more than 50 different crRNAs, whose stability and maintenance critically depend on the proteins Cas5 and Cas7, which bind the crRNA and form the Cascade complex...
April 13, 2018: RNA Biology
Cheolwon Choi, Seulgi Yoon, Hyesu Moon, Yun-Ui Bae, Chae-Bin Kim, Penchatr Diskul-Na-Ayudthaya, Trinh Van Ngu, Javaria Munir, JaeWook Han, Se Bin Park, Jong-Seok Moon, Sujung Song, Seongho Ryu
Techniques to isolate the small RNA fraction (<200nt) by column-based methods are commercially available. However, their use is limited because of the relatively high cost. We found that large RNA molecules, including mRNAs and rRNAs, are aggregated together in the presence of salts when RNA pellets are over-dried. Moreover, once RNA pellets are over-dried, large RNA molecules are barely soluble again during the elution process, whereas small RNA molecules (<100nt) can be eluted. We therefore modified the acid guanidinium thiocyanate-phenol-chloroform (AGPC)-based RNA extraction protocol by skipping the 70% ethanol washing step and over-drying the RNA pellet for 1 hour at room temperature...
April 11, 2018: RNA Biology
Tong Guo, Wenyuan Han, Qunxin She
Sulfolobus islandicus Rey15A encodes one type I-A and two type III-B systems, all of which are active in mediating nucleic acids interference. However, the effectiveness of each CRISPR system against virus infection was not tested in this archaeon. Here we constructed S. islandicus strains that constitutively express the antiviral immunity from either I-A, or III-B, or I-A plus III-B systems against SMV1 and tested the response of each host to SMV1 infection. We found that, although both CRISPR immunities showed a strongly inhibition to viral DNA replication at an early stage of incubation, the host I-A CRISPR immunity gradually lost the control on virus proliferation, allowing accumulation of cellular viral DNA and release of a large number of viral particles...
April 9, 2018: RNA Biology
Daniel J Luciano, Nikita Vasilyev, Jamie Richards, Alexander Serganov, Joel G Belasco
Deprotection of the 5' end appears to be a universal mechanism for triggering the degradation of mRNA in bacteria and eukaryotes. In Escherichia coli, for example, converting the 5' triphosphate of primary transcripts to a monophosphate accelerates cleavage at internal sites by the endonuclease RNase E. Previous studies have shown that the RNA pyrophosphohydrolase RppH catalyzes this transformation in vitro and generates monophosphorylated decay intermediates in vivo. Recently, we reported that purified E. coli RppH unexpectedly reacts faster with diphosphorylated than with triphosphorylated substrates...
April 5, 2018: RNA Biology
Xing Chen, Zhihan Zhou, Yan Zh Ao
Recently, accumulating evidences have indicated miRNAs play critical roles in the progression and development of various human complex diseases, which pointed out that identifying miRNA-disease association could enable us to understand diseases at miRNA level. Thus, revealing more and more potential miRNA-disease associations is a vital topic in biomedical domain. However, it will be extremely expensive and time-consuming if we examine all the possible miRNA-disease pairs. Therefore, more accurate and efficient methods are being highly requested to detect potential miRNA-disease associations...
April 5, 2018: RNA Biology
Federico Gaiti, Bernard M Degnan, Miloš Tanurdžić
How animals evolved from a single-celled ancestor over 700 million years ago is poorly understood. Recent transcriptomic and chromatin analyses in the sponge Amphimedon queenslandica, a morphologically-simple representative of one of the oldest animal phyletic lineages, have shed light on what innovations in the genome and its regulation underlie the emergence of animal multicellularity. Comparisons of the regulatory genome of this sponge with those of more complex bilaterian model species and even simpler unicellular relatives have revealed that fundamental changes in genome regulatory complexity accompanied the evolution of animal multicellularity...
April 4, 2018: RNA Biology
Luis M Vaschetto
Transfection of small non-coding RNAs (sncRNAs) molecules has become a routine technique widely used for silencing gene expression by triggering post-transcriptional and transcriptional RNA interference (RNAi) pathways. Moreover, in the past decade, small activating (saRNA) sequences targeting promoter regions were also reported, thereby a RNA-based gene activation (RNAa) mechanism has been proposed. In this regard, Turner and colleagues recently discovered an endogenous microRNA (miRNA) which binds its promoter in order to upregulate its own expression...
April 3, 2018: RNA Biology
Laurène Bastet, Pierre Turcotte, Joseph T Wade, Daniel A Lafontaine
Riboswitches are RNA regulators that control gene expression by modulating their structure in response to metabolite binding. The study of mechanisms by which riboswitches modulate gene expression is crucial to understand how riboswitches are involved in maintaining cellular homeostasis. Previous reports indicate that riboswitches can control gene expression at the level of translation, transcription or mRNA decay. However, there are very few described examples where riboswitches regulate multiple steps in gene expression...
April 3, 2018: RNA Biology
Huan Hu, Li Zhang, Haixin Ai, Hui Zhang, Yetian Fan, Qi Zhao, Hongsheng Liu
LncRNA plays an important role in many biological and disease progression by binding to related proteins. However, the experimental methods for studying lncRNA-protein interactions are time-consuming and expensive. Although there are a few models designed to predict the interactions of ncRNA-protein, they all have some common drawbacks that limit their predictive performance. In this study, we present a model called HLPI-Ensemble designed specifically for human lncRNA-protein interactions. HLPI-Ensemble adopts the ensemble strategy based on three mainstream machine learning algorithms of Support Vector Machines (SVM), Random Forests (RF) and Extreme Gradient Boosting (XGB) to generate HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB Ensemble, respectively...
March 27, 2018: RNA Biology
Kirtika H Asrani, Jeremiah D Farelli, Mary R Stahley, Rebecca L Miller, Christopher J Cheng, Romesh R Subramanian, Jeffrey M Brown
mRNA based therapies hold great promise for the treatment of genetic diseases. However, this therapeutic approach suffers from multiple challenges including the short half-life of exogenously administered mRNA and subsequent protein production. Modulation of untranslated regions (UTR) represents one approach to enhance both mRNA stability and translation efficiency. The current studies describe and validate screening methods using a diverse set of 5'UTR and 3'UTR combinations for improved expression of the Arginase 1 (ARG1) protein, a potential therapeutic mRNA target...
March 26, 2018: RNA Biology
Rabea Jesser, Juliane Behler, Christian Benda, Viktoria Reimann, Wolfgang R Hess
Specialized RNA endonucleases are critical for efficient activity of the CRISPR-Cas defense mechanisms against invading DNA or RNA. Cas6-type enzymes are the RNA endonucleases in many type I and type III CRISPR-Cas systems. These enzymes are diverse and critical residues involved in the recognition and cleavage of RNA substrates are not universally conserved. Cas6 endonucleases associated with the CRISPR-Cas subtypes I-A, I-B, I-C, I-E and I-F, as well as III-B have been studied from three archaea and four bacteria thus far...
March 26, 2018: RNA Biology
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