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RNA Biology

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https://www.readbyqxmd.com/read/28145797/characterisation-of-new-generation-aminoglycoside-promoting-premature-termination-codon-readthrough-in-cancer-cells
#1
Laure Bidou, Olivier Bugaud, Valery Belakhov, Timor Baasov, Olivier Namy
Nonsense mutations, generating premature termination codons (PTCs), account for 10% to 30% of the mutations in tumour suppressor genes. Nonsense translational suppression, induced by small molecules including gentamicin and G418, has been suggested as a potential therapy to counteract the deleterious effects of nonsense mutations in several genetic diseases and cancers. We describe here that NB124, a synthetic aminoglycoside derivative recently developed especially for PTC suppression, strongly induces apoptosis in human tumour cells by promoting high level of PTC readthrough...
February 1, 2017: RNA Biology
https://www.readbyqxmd.com/read/28136159/crispr-cas-type-ii-based-synthetic-biology-applications-in-eukaryotic-cells
#2
Mario Andrea Marchisio, Zhiwei Huang
The CRISPR-Cas system has rapidly reached a huge popularity as a new, powerful method for precise DNA editing and genome reengineering. In Synthetic Biology, the CRISPR-Cas type II system has inspired the construction of a novel class of RNA-based transcription factors. In their simplest form, they are made of a CRISPR RNA molecule, which targets a promoter sequence, and a deficient Cas9 (i.e. deprived of any nuclease activity) that has been fused to an activation or a repression domain. Up- and down-regulation of single genes in mammalian and yeast cells have been achieved with satisfactory results...
January 31, 2017: RNA Biology
https://www.readbyqxmd.com/read/28125361/rna-mediated-communication-between-helminths-and-their-hosts-the-missing-links
#3
Julie Claycomb, Cei Abreu-Goodger, Amy H Buck
Small RNAs have been discovered in a wide variety of extracellular environments and are now thought to participate in communication between cells and even between different organisms and species. Helminths are parasitic worms that generally reside in extracellular niches in their hosts and can establish chronic infection through the release of immunomodulatory factors. Recent work has demonstrated that Extracellular RNA (exRNA) may be another class of immunomodulator secreted by helminths. Here we will detail what is known about small RNA pathways in helminth pathogens (focusing on nematodes) and mammalian hosts...
January 26, 2017: RNA Biology
https://www.readbyqxmd.com/read/28121234/human-m-6-a-writers-two-subunits-two-roles
#4
Xiang Wang, Jinbo Huang, Tingting Zou, Ping Yin
Cellular RNAs with diverse chemical modifications have been observed, and N(6)-methyladenosine (m(6)A) is one of the most abundant internal modifications found on mRNA and non-coding RNAs, playing a vital role in diverse biological processes. In humans, m(6)A modification is catalyzed by the METTL3-METTL14 methyltransferase complex, which is regulated by WTAP and another factor. Three groups have recently and independently reported the structure of this complex with or without cofactors. Here, we focus on the detailed mechanism of the m(6)A methyltransferase complex and the properties of each subunit...
January 25, 2017: RNA Biology
https://www.readbyqxmd.com/read/28102759/antisense-transcription-of-the-myotonic-dystrophy-locus-yields-low-abundant-rnas-with-and-without-cag-n-repeat
#5
Anke E E G Gudde, Simon J van Heeringen, Amanda I de Oude, Ingeborg D G van Kessel, Joseph Estabrook, Eric T Wang, Bé Wieringa, Derick G Wansink
The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the DMPK gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3' UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biological significance of this antisense gene (DM1-AS) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that DM1-AS spans >6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat...
January 19, 2017: RNA Biology
https://www.readbyqxmd.com/read/28095188/mir-148a-and-mir-17-5p-synergistically-regulate-milk-tag-synthesis-via-ppargc1a-and-ppara-in-goat-mammary-epithelial-cells
#6
Zhi Chen, Jun Luo, Shuang Sun, Duoyao Cao, Huaiping Shi, Juan J Loor
MicroRNA (miRNA) are a class of '18-25' nt RNA molecules which regulate gene expression and play an important role in several biological processes including fatty acid metabolism. Here we utilized S-Poly (T) and high-throughput sequencing to evaluate the expression of miRNA and mRNA during early-lactation and in the non-lactating ("dry") period in goat mammary gland tissue. Results indicated that miR-148a, miR-17-5p, PPARGC1A and PPARA are highly expressed in the goat mammary gland in early-lactation and non-lactating periods...
January 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28095181/how-trnas-dictate-nuclear-codon-reassignments-only-a-few-can-capture-non-cognate-codons
#7
Martin Kollmar, Stefanie Mühlhausen
Messenger RNA decoding by tRNAs and tRNA charging by aminoacyl-tRNA synthetases are biochemically separated processes that nevertheless in general involve the same nucleotides. The combination of charging and decoding determines the genetic code. Codon reassignment happens when a differently charged tRNA replaces a former cognate tRNA. The recent discovery of the polyphyly of the yeast CUG sense codon reassignment challenged previous mechanistic considerations and led to the proposal of the so-called tRNA loss driven codon reassignment hypothesis...
January 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28095120/the-bent-conformation-of-poly-a-binding-protein-induced-by-rna-binding-is-required-for-its-translational-activation-function
#8
Ka Young Hong, Seung Hwan Lee, Sohyun Gu, Eunah Kim, Sihyeon An, Junyoung Kwon, Jong-Bong Lee, Sung Key Jang
A recent study revealed that poly(A)-binding protein (PABP) bound to poly(A) RNA exhibits a sharply bent configuration at the linker region between RNA-recognition motif 2 (RRM2) and RRM3, whereas free PABP exhibits a highly flexible linear configuration. However, the physiological role of the bent structure of mRNA-bound PABP remains unknown. We investigated a role of the bent structure of PABP by constructing a PABP variant that fails to form the poly(A)-dependent bent structure but maintains its poly(A)-binding activity...
January 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28085550/microrna-432-targeting-e2f3-and-p55pik-inhibits-myogenesis-through-pi3k-akt-mtor-signaling-pathway
#9
Meilin Ma, Xiangming Wang, Xiaochang Chen, Rui Cai, Fenfen Chen, Wuzi Dong, Gongshe Yang, Weijun Pang
Skeletal muscle is the dominant executant in locomotion and regulator in energy metabolism. Embryonic myogenesis and postnatal muscle growth are controlled by a cascade of transcription factors and epigenetic regulatory mechanisms. MicroRNAs (miRNAs), a family of non-coding RNA of 22 nucleotides in length, post-transcriptionally regulates expression of mRNA by pairing the seed sequence to 3' UTR of target mRNA. Increasing evidence has demonstrated that miRNAs are important regulators in diverse myogenic processes...
January 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/28080204/identification-of-hur-target-circular-rnas-uncovers-suppression-of-pabpn1-translation-by-circpabpn1
#10
Kotb Abdelmohsen, Amaresh C Panda, Rachel Munk, Ioannis Grammatikakis, Dawood B Dudekula, Supriyo De, Jiyoung Kim, Ji Heon Noh, Kyoung Mi Kim, Jennifer L Martindale, Myriam Gorospe
HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analyses revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA...
January 12, 2017: RNA Biology
https://www.readbyqxmd.com/read/28067598/why-so-narrow-distribution-of-anti-sense-regulated-type-i-toxin-antitoxin-systems-compared-with-type-ii-and-type-iii-systems
#11
Dorien S Coray, Nicole E Wheeler, Jack A Heinemann, Paul P Gardner
Toxin-antitoxin (TA) systems are gene modules that appear to be horizontally mobile across a wide range of prokaryotes. It has been proposed that type I TA systems, with an antisense RNA-antitoxin, are less mobile than other TAs that rely on direct toxin-antitoxin binding but no direct comparisons have been made. We searched for type I, II and III toxin families using iterative searches with profile hidden Markov models across phyla and replicons. The distribution of type I toxin families were comparatively narrow, but these patterns weakened with recently discovered families...
January 9, 2017: RNA Biology
https://www.readbyqxmd.com/read/28059623/coordinating-cell-cycle-regulated-histone-gene-expression-through-assembly-and-function-of-the-histone-locus-body
#12
Robert J Duronio, William F Marzluff
Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and pre-mRNA processing...
January 6, 2017: RNA Biology
https://www.readbyqxmd.com/read/28045588/global-decay-of-mrna-is-a-hallmark-of-apoptosis-in-aging-xenopus-eggs
#13
Alexander A Tokmakov, Sho Iguchi, Tetsushi Iwasaki, Yasuo Fukami, Ken-Ichi Sato
Cytoplasmic mRNAs are specifically degraded in somatic cells as a part of early apoptotic response. However, no reports have been presented so far concerning mRNA fate in apoptotic gametes. In the present study, we analyzed the content of various cytoplasmic mRNAs in aging oocytes and eggs of the African clawed frog, Xenopus laevis. To circumvent large gene expression variation among the individual oocytes and eggs, single-cell monitoring of transcript levels has been implemented, using multiple cytoplasmic collections and reverse transcriptase quantitative PCR...
January 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/28045575/eukaryotic-stand-alone-pseudouridine-synthases-rna-modifying-enzymes-and-emerging-regulators-of-gene-expression
#14
Anne C Rintala-Dempsey, Ute Kothe
For a long time, eukaryotic stand-alone pseudouridine synthases (Pus enzymes) were neglected as non-essential enzymes adding seemingly simple modifications to tRNAs and small nuclear RNAs. Most studies were limited to the identification and initial characterization of the yeast Pus enzymes. However, recent transcriptome-wide mapping of pseudouridines in yeast and humans revealed pervasive modification of mRNAs and other non-coding RNAs by Pus enzymes which is dynamically regulated in response to cellular stress...
January 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/28045572/rna-seq-unveils-new-attributes-of-the-heterogeneous-salmonella-host-cell-communication
#15
Francisco García-Del Portillo, M Graciela Pucciarelli
High-throughput RNA sequencing (RNA-Seq) has uncovered hundreds of small RNAs and complex modes of RNA regulation in every bacterium analyzed to date. This complexity agrees with the adaptability of most bacteria to varied environments including, in the case of pathogens, the new niches encountered in the host. Recent RNA-Seq studies have analyzed simultaneously gene expression in the intracellular pathogen Salmonella enterica and infected host cells at population and single-cell level. Distinct polarization states or interferon responses in the infected macrophage were linked to variable growth rates or activities of defined virulence regulators in intra-phagosomal bacteria...
January 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/28027000/viroid-quasispecies-revealed-by-deep-sequencing
#16
Joseph R J Brass, Robert A Owens, Jaroslav Matoušek, Gerhard Steger
Viroids are non-coding single-stranded circular RNA molecules that replicate autonomously in infected host plants causing mild to lethal symptoms. Their genomes contain about 250-400 nucleotides, depending on viroid species. Members of the family Pospiviroidae, like the Potato spindle tuber viroid (PSTVd), replicate via an asymmetric rolling-circle mechanism using the host DNA-dependent RNA-Polymerase II in the nucleus, while members of Avsunviroidae are replicated in a symmetric rolling-circle mechanism probably by the nuclear-encoded polymerase in chloroplasts...
December 27, 2016: RNA Biology
https://www.readbyqxmd.com/read/28010188/the-in-vivo-genetic-toolkit-for-studying-expression-and-functions-of-drosophila-melanogaster-micrornas
#17
Hina Iftikhar, Janna N Schultzhaus, Chloe J Bennett, Ginger E Carney
Since the initial reports that a group of small RNAs, now known as microRNAs (miRNAs), regulates gene expression without being translated into proteins, there has been an explosion of studies on these important expression modulators. Drosophila melanogaster has proven to be one of the most amenable animal models for investigations of miRNA biogenesis and gene regulatory activities. Here, we highlight the publicly available genetic tools and strategies for in vivo functional studies of miRNA activity in D. melanogaster...
December 23, 2016: RNA Biology
https://www.readbyqxmd.com/read/28010172/rna-biology-of-angiogenin-current-state-and-perspectives
#18
Shawn M Lyons, Marta M Fay, Yasutoshi Akiyama, Paul Anderson, Pavel Ivanov
Angiogenin (ANG) is a secreted ribonuclease best known for its ability to promote formation of blood vessels. Extensive research over many years has elucidated its structure and biophysical properties, although our knowledge of molecular mechanisms underlying ANG-associated biological processes remained limited. Intriguingly, many of these processes require the ribonuclease activity of ANG, thus highlighting the importance of identifying and characterizing RNA targets and intermediates of ANG-mediated endonucleolytic cleavage...
December 23, 2016: RNA Biology
https://www.readbyqxmd.com/read/28010165/modular-arrangement-of-regulatory-rna-elements
#19
Johanna Roßmanith, Franz Narberhaus
Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities...
December 23, 2016: RNA Biology
https://www.readbyqxmd.com/read/28005467/defining-the-purity-of-exosomes-required-for-diagnostic-profiling-of-small-rna-suitable-for-biomarker-discovery
#20
Camelia Quek, Shayne A Bellingham, Chol-Hee Jung, Benjamin J Scicluna, Mitch C Shambrook, Robyn A Sharples, Lesley Cheng, Andrew F Hill
Small non-coding RNAs (ncRNA), including microRNAs (miRNA), enclosed in exosomes are being utilised for biomarker discovery in disease. Two common exosome isolation methods involve differential ultracentrifugation or differential ultracentrifugation coupled with Optiprep gradient fractionation. Generally, the incorporation of an Optiprep gradient provides better separation and increased purity of exosomes. The question of whether increased purity of exosomes is required for small ncRNA profiling, particularly in diagnostic and biomarker purposes, has not been addressed and highly debated...
December 22, 2016: RNA Biology
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