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RNA Biology

Martin Porsch, Esra Özdemir, Martin Wisniewski, Sebastian Graf, Fabian Bull, Katrin Hoffmann, Atanas Ignatov, Johannes Haybaeck, Ivo Große, Thomas Kalinski, Norbert Nass
Acquired tamoxifen resistance is a persistent problem for the treatment of estrogen receptor positive, premenopausal breast cancer patients and predictive biomarkers are still elusive. We here analyzed gene expression changes in a cellular model to identify early and late changes upon tamoxifen exposure and thereby novel prognostic biomarkers. Estrogen receptor positive MCF-7 cells were incubated with 4OH-tamoxifen (10 nM) and gene expression analyzed by array hybridization during 12 weeks. Array results were confirmed by nCounter- and qRT-PCR technique...
February 13, 2019: RNA Biology
Bingning Xie, Emmanuelle Becker, Igor Stuparevic, Maxime Wery, Ugo Szachnowski, Antonin Morillon, Michael Primig
5-fluorouracil (5-FU) was isolated as an inhibitor of thymidylate synthase, which is important for DNA synthesis. The drug was later found to also affect the conserved 3'-5' exoribonuclease EXOSC10/Rrp6, a catalytic subunit of the RNA exosome that degrades and processes protein-coding and non-coding transcripts. Work on 5-FU's cytotoxicity has been focused on mRNAs and non-coding transcripts such as rRNAs, tRNAs and snoRNAs. However, the effect of 5-FU on long non-coding RNAs (lncRNAs), which include regulatory transcripts important for cell growth and differentiation, is poorly understood...
February 13, 2019: RNA Biology
M Moreno, L Vázquez, A López-Carrasco, J A Martín-Gago, R Flores, C Briones
Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques...
February 8, 2019: RNA Biology
Jack Common, Edze R Westra
Population bottlenecks often cause strong reductions in genetic diversity and alter population structure. In the context of host-parasite interactions, bottlenecks could in theory benefit either the host or the pathogen. We predicted that bottlenecking of bacterial populations that evolve CRISPR immunity against bacteriophages (phage) would benefit the pathogen, because CRISPR spacer diversity can rapidly drive phages extinct. To test this, we bottlenecked populations of bacteria and phage, tracking phage persistence and the evolution of bacterial resistance mechanisms...
February 5, 2019: RNA Biology
Joseph A Ross, Mette Thorsing, Eva Maria Sternkopf Lillebæk, Patrícia Teixeira Dos Santos, Birgitte H Kallipolitis
The bacterial pathogen Listeria monocytogenes encodes seven homologous small regulatory RNAs, named the LhrC family of sRNAs. The LhrCs are highly induced under infection-relevant conditions and are known to inhibit the expression of multiple target mRNAs encoding virulence-associated surface proteins. In all cases studied so far, the LhrCs use their CU-rich regions for base pairing to complementary AG-rich sequences of the ribosomal binding site (RBS) of specific target mRNAs. Consequently, LhrC-mRNA interaction results in inhibition of translation followed by mRNA degradation, corresponding to the canonical model for sRNA-mediated gene regulation in bacteria...
February 1, 2019: RNA Biology
Cinta Pegueroles, Susana Iraola-Guzmán, Uciel Chorostecki, Ewa Ksiezopolska, Ester Saus, Toni Gabaldón
Long non-coding RNAs (lncRNAs) are a heterogeneous class of genes that do not code for proteins. Since lncRNAs (or a fraction thereof) are expected to be functional, many efforts have been dedicated to catalog lncRNAs in numerous organisms, but our knowledge of lncRNAs in non vertebrate species remains very limited. Here, we annotated lncRNAs using transcriptomic data from the same larval stage of four Caenorhabditis species. The number of annotated lncRNAs in self-fertile nematodes was lower than in out-crossing species...
January 29, 2019: RNA Biology
Patrícia de Cássia Ruy, Natália Melquie Monteiro Teles, Rubens Daniel Miserani Magalhães, Felipe Freitas de Castro, Leandro Dias, Tania Paula Aquino Defina, Elton José Rosas de Vasconcelos, Peter J Myler, Angela Kaysel Cruz
Leishmaniasis is a worldwide public health problem caused by protozoan parasites of the genus Leishmania. Leishmania braziliensis is the most important species responsible for tegumentary leishmaniases in Brazil. An understanding of the molecular mechanisms underlying the success of this parasite is urgently needed. An in-depth study on the modulation of gene expression across the life cycle stages of L. braziliensis covering coding and noncoding RNAs (ncRNAs) was missing and is presented herein. Analyses of differentially expressed (DE) genes revealed that most prominent differences were observed between the transcriptomes of insect and mammalian proliferative forms (6,576 genes)...
January 28, 2019: RNA Biology
Guoyun Zhang, Songfeng Diao, Tong Zhang, Daoguo Chen, Caiyun He, Jianguo Zhang
As a rising star of noncoding RNA, circular RNAs (circRNAs) have a covalently closed loop structure, which formed by 3'-5' ligation during splicing. A few circRNAs were identified and thought to be transcriptional noise due to cognitive defect over the past 40 years. Recently, with the development of high-throughput RNA sequencing techniques and specific algorithms for circRNA detection and quantification, plenty of potential circRNAs were identified in many species which play important roles in various biological processes...
January 25, 2019: RNA Biology
Wei Wang, Dan Liu, Dongdong Chen, Yingying Cheng, Xiaopei Zhang, Lirong Song, Mengjiao Hu, Jie Dong, Fafu Shen
Salinity stress is a major abiotic stress affecting the productivity and fiber quality of cotton. Although reactive oxygen species (ROS) play critical roles in plant stress responses, their complex molecular regulatory mechanism under salinity stress is largely unknown in cotton, especially microRNA (miRNA)-mediated regulation of superoxide dismutase gene expression. Here, we report that a cotton iron superoxide dismutase gene GhFSD1 and the cotton miRNA ghr-miR414c work together in response to salinity stress...
January 24, 2019: RNA Biology
Chang Tang, Hua Zhou, Xiao Zheng, Yanming Zhang, Xiaofeng Sha
Since lots of miRNA-disease associations have been verified, it is meaningful to discover more miRNA-disease associations for serving disease diagnosis and prevention of human complex diseases. However, it is not practical to identify potential associations using traditional biological experimental methods since the process is expensive and time consuming. Therefore, it is necessary to develop efficient computational methods to accomplish this task. In this work, we introduced a matrix completion model with dual Laplacian regularization (DLRMC) to infer unknown miRNA-disease associations in heterogeneous omics data...
January 24, 2019: RNA Biology
Amit Gautam, Jean D Beggs
Snu114, a component of the U5 snRNP, plays a key role in activation of the spliceosome. It controls the action of Brr2, an RNA-stimulated ATPase/RNA helicase that disrupts U4/U6 snRNA base-pairing prior to formation of the spliceosome's catalytic centre. Snu114 has a highly conserved domain structure that resembles that of the GTPase EF-2/EF-G in the ribosome. It has been suggested that the regulatory function of Snu114 in activation of the spliceosome is mediated by its C-terminal region, however, there has been only limited characterisation of the interactions of the C-terminal domains...
January 23, 2019: RNA Biology
Sunil More, Zhengyu Zhu, Kong Lin, Chaoqun Huang, Samuel Pushparaj, Yurong Liang, Roshini Sathiaseelan, Xiaoyun Yang, Lin Liu
Long non-coding RNAs (lncRNAs) are a new arm of gene regulatory mechanism as discovered by sequencing techniques and follow-up functional studies. There are only few studies on lncRNAs as related to gene expression regulation and anti-viral activity during influenza virus infection. We sought to identify and characterize lncRNAs involved in influenza virus replication. Using RNA sequencing analysis, we found that 1,912 lncRNAs were significantly changed in human lung epithelial A549 cells infected with influenza A/Puerto Rico/8/34...
January 22, 2019: RNA Biology
Francisco Ferreira Duarte Junior, Paulo Sérgio Alves Bueno, Sofia L Pedersen, Fabiana Dos Santos Rando, José Renato Pattaro Júnior, Daniel Caligari, Anelise Cardoso Ramos, Lorena Gomes Polizelli, Ailson Francisco Dos Santos Lima, Quirino Alves de Lima Neto, Torsten Krude, Flavio Augusto Vicente Seixas, Maria Aparecida Fernandez
Non-coding Y RNAs and stem-bulge RNAs are homologous small RNAs in vertebrates and nematodes, respectively. They share a conserved function in the replication of chromosomal DNA in these two groups of organisms. However, functional homologues have not been found in insects, despite their common early evolutionary history. Here, we describe the identification and functional characterization of two sbRNAs in Drosophila melanogaster, termed Dm1 and Dm2. The genes coding for these two RNAs were identified by a computational search in the genome of D...
January 22, 2019: RNA Biology
Linah Mahmoud, Walid Moghrabi, Khalid S A Khabar, Edward G Hitti
AU-rich elements (AREs) are cis-acting instability and translation inhibition elements that are present in the 3'UTR of most inducible inflammatory mRNAs such as TNF and Cxcl2. mRNAs that contain AREs are, by default, repressed and only transiently expressed in response to stimuli. They are targeted by the inducible RNA-binding protein Tristetraprolin (TTP) which blocks their translation and facilitates their decay, thereby contributing to the quick termination of their expression. The exogenous over-expression of TTP in HEK293 cells can unexpectedly lead to the upregulation and extended expression of a nanoLuciferase reporter that contains the ARE of TNF...
January 21, 2019: RNA Biology
Xu-Feng Xu, You-Cui Wang, Liang Zong, Xiao-Long Wang
Long-term memory formation requires gene expression and new protein synthesis. MicroRNAs (miRNAs), a family of small non-coding RNAs that inhibit target gene mRNA expression, are involved in new memory formation. In this study, elevated miR-151-5p (miR-151) levels were found to be responsible for hippocampal contextual fear memory formation. Using a luciferase reporter assay, we demonstrated that miR-151 targets APH1a, a protein that has been identified as a key factor in γ-secretase activity, namely APH1a...
January 21, 2019: RNA Biology
Martin Müller, Anke Samel-Pommerencke, Carine Legrand, Francesca Tuorto, Frank Lyko, Ann E Ehrenhofer-Murray
Enzymes of the cytosine-5 RNA methyltransferase Trm4/NSun2 family methylate tRNAs at C48 and C49 in multiple tRNAs, as well as C34 and C40 in selected tRNAs. In contrast to most other organisms, fission yeast Schizosaccharomyces pombe carries two Trm4/NSun2 homologs, Trm4a (SPAC17D4.04) and Trm4b (SPAC23C4.17). Here, we have employed tRNA methylome analysis to determine the dependence of cytosine-5 methylation (m5 C) tRNA methylation in vivo on the two enzymes. Remarkably, Trm4a is responsible for all C48 methylation, which lies in the tRNA variable loop, as well as for C34 in tRNALeu CAA and tRNAPro CGG , which are at the anticodon wobble position...
January 15, 2019: RNA Biology
Chun-Chun Wang, Xing Chen, Jun Yin, Jia Qu
MicroRNAs (miRNAs) play an important role in prevention, diagnosis and treatment of human complex diseases. Predicting potential miRNA-disease associations could provide important prior information for medical researchers. Therefore, reliable computational models are expected to be an effective supplement for inferring associations between miRNAs and diseases. In this study, we developed a novel calculative model named Negative Samples Extraction based MiRNA-Disease Association prediction (NSEMDA). NSEMDA filtered reliable negative samples by two positive-unlabeled learning models, namely, the Spy and Rocchio techniques and calculated similarity weights for ambiguous samples...
January 15, 2019: RNA Biology
Siyu Luan, Junyun Luo, Hui Liu, Zhaoyong Li
DIS3L2, in which mutations have been linked to Perlman syndrome, is an RNA-binding protein with 3'-5' exoribonuclease activity. It contains two CSD domains and one S1 domain, all of which are RNA-binding domains, and one RNB domain that is responsible for the exoribonuclease activity. The 3' polyuridine of RNA substrates can serve as a degradation signal for DIS3L2. Because DIS3L2 is predominantly localized in the cytoplasm, it can recognize, bind, and mediate the degradation of cytoplasmic uridylated RNA, including pre-microRNA, mature microRNA, mRNA, and some other non-coding RNAs...
January 13, 2019: RNA Biology
Katherine Elizabeth Sloan, Andrew Alexander Knox, Graeme Raymond Wells, Claudia Schneider, Nicholas James Watkins
Ribosome production is an essential cellular process involving a plethora of trans-acting factors, such as nucleases, methyltransferases, RNA helicases and kinases that catalyse key maturation steps. Precise temporal and spatial regulation of such enzymes is essential to ensure accurate and efficient subunit assembly. Here, we focus on the maturation of the 3' end of the 18S rRNA in human cells. We reveal that human RIO2 is an active kinase that phosphorylates both itself and the rRNA methyltransferase DIM1 in vitro...
January 13, 2019: RNA Biology
Xin Pang, Zhixia Zhou, Zhuang Yu, Lichun Han, Zhijuan Lin, Xiang Ao, Chang Liu, Yuqi He, Murugavel Ponnusamy, Peifeng Li, Jianxun Wang
The development of chemotherapeutic drugs resistance such as doxorubicin (DOX) and cisplatin (DDP) is the major barrier in gastric cancer therapy. Emerging evidences reveal that microRNAs (miRNAs) contribute to chemosensitivity. In this study, we investigated the role of miR-633, an oncogenic miRNA, in gastric cancer chemoresistance. In gastric cancer tissue and cell lines, miR-633 expression was highly increased and correlated with down regulation of Fas-associated protein with death domain (FADD). Inhibition of miR-633 significantly increased FADD protein level and enhanced DOX/DDP induced apoptosis in vitro...
January 10, 2019: RNA Biology
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