Podcasts about ncrna

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.24.536852v1?rss=1 Authors: Zeidler, M., Tavares-Ferreira, D., Brougher, J., Price, T. J., Kress, M. Abstract: Non-coding RNAs (ncRNAs) play a critical role in regulating gene expression during development and in the pathogenesis of diseases. In particular, microRNAs have been extensively studied in the context of neurogenesis, the differentiation of pain sensing nociceptive neurons and the pathogenesis of pain disorder, however, little is known about the developmental signatures of other ncRNA species throughout sensory neuron differentiation. Moreover, there is currently no information available about the general expression signatures of ncRNAs in human dorsal root ganglia (DRGs) harboring the cell bodies of primary afferent nociceptors. To bridge this knowledge gap, we developed a comprehensive atlas of small ncRNA species signatures during the differentiation of human induced pluripotent stem cell (iPSC)-derived nociceptive neurons. By employing a combination of iPSC-derived sensory neuron and human DRG long and short RNA co-sequencing, we identified specific signatures that describe the developmental processes and the sig-natures of all currently known small ncRNA species in detail. Our analysis revealed that different ncRNA species, including tRNAs, snoRNAs, lncRNAs, and piRNAs, are associated with different stages of sensory neuron differentiation and maturation. We retrieved pro-nounced similarities in ncRNA expression between human DRG and late-stage iPSC-derived sensory neurons, which further supports the use of iPSC-derived sensory neurons to uncover functional and regulatory changes in ncRNAs and their suitability as a as a human model system to bridge the transla-tional gap between preclinical findings mostly from rodent models and our understanding of human disorders for the development of mechanism-based treatments. In summary, our findings provide important insights into the role of ncRNA species other than microRNAs in human nociceptors. The updated NOCICEPTRA2.0 Tool will be the first fully comprehensive searchable ncRNA database for human sensory neurons enabling researchers to investigate important hub ncRNA regulators in nociceptors in full detail. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.27.315507v1?rss=1 Authors: Liu, B., Thippabhotla, S., Zhang, J., Zhong, C. Abstract: Noncoding RNA plays important regulatory and functional roles in microorganisms, such as gene expression regulation, signaling, protein synthesis, and RNA processing. Given its essential role in microbial physiology, it is natural to question whether we can use noncoding RNAs as biomarkers to distinguish among environments under different biological conditions, such as those between healthy versus disease status. The current metagenomic sequencing technology primarily generates short reads, which contain incomplete structural information that may complicate noncoding RNA homology detection. On the other hand, de novo assembly of the metagenomics sequencing data remains fragmentary and has a risk of missing low-abundant noncoding RNAs. To tackle these challenges, we have developed DRAGoM (Detection of RNA using Assembly Graph from Metagenomics data), a novel noncoding RNA homology search algorithm. DRAGoM operates on a metagenome assembly graph, rather than on unassembled reads or assembled contigs. Our benchmark experiments show DRAGoM's improved performance and robustness over the traditional approaches. We have further demonstrated DRAGoM's real-world applications in disease characterization via analyzing a real case-control gut microbiome dataset for Type-2 diabetes (T2D). DRAGoM revealed potential ncRNA biomarkers that can clearly separate the T2D gut microbiome from those of healthy controls. DRAGoM is freely available from https://github.com/benliu5085/DRAGoM. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.10.290924v1?rss=1 Authors: Sweeney, B. A., Hoksza, D., Nawrocki, E. P., Ribas, C. E., Madeira, F., Cannone, J. J., Gutell, R. R., Maddala, A., Meade, C., Williams, L. D., Petrov, A. S., Chan, P. P., Lowe, T. M., Finn, R. D., Petrov, A. I. Abstract: Non-coding RNAs (ncRNA) are essential for all life, and the functions of many ncRNAs depend on their secondary (2D) and tertiary (3D) structure. Despite proliferation of 2D visualisation software, there is a lack of methods for automatically generating 2D representations in consistent, reproducible, and recognisable layouts, making them difficult to construct, compare and analyse. Here we present R2DT, a comprehensive method for visualising a wide range of RNA structures in standardised layouts. R2DT is based on a library of 3,632 templates representing the majority of known structured RNAs, from small RNAs to the large subunit ribosomal RNA. R2DT has been applied to ncRNA sequences from the RNAcentral database and produced >13 million diagrams, creating the world's largest RNA 2D structure dataset. The software is freely available at https://github.com/rnacentral/R2DT and a web server is found at https://rnacentral.org/r2dt. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.16.087395v1?rss=1 Authors: Asgari, Y., Heng, J. I.-T., Lovell, N., Forrest, A., Alinejad-Rokny, H. Abstract: Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment and in diseases is poorly understood. In this study, we have performed a genome-wide investigation of human noncoding RNAs for cell regulatory functions in brain tissue. By analysing ENCODE regulatory features, associations with FANTOM5 tissue-specific enhancers, as well as tissue-specific expression profiles, we have identified 17,743 noncoding RNAs comprising at least one nervous system-related expression Quantitative Trait Loci (eQTL) polymorphism that is associated with protein coding genes. Of these, 908 brain-enriched noncoding RNAs (comprising 907 long noncoding RNAs and 1 pseudogene) also overlap with chromatin states characterised as enhancers. Based on these criteria, we referred to such noncoding RNAs with putative enhancer activity as brain "enhancer-ncRNAs". To investigate their impact in neurodevelopmental disorders, we integrated GWAS SNPs and Copy Number Variation (CNV) data and found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs. However, in 23 of these 82 enhancer-ncRNAs, eQTL interaction was explained solely by the presence of each of these noncoding RNAs, suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. We also cross-referenced our data with the DECIPHER database of clinical phenotypes to find that mutations to 34 of the 82 enhancer-ncRNAs are significantly associated with phenotypes including behavioural abnormality, and cognitive impairment. Taken together, we provide evidence for a distinct set of brain-enriched ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders. Copy rights belong to original authors. Visit the link for more info

「わたしは人類」と「柿ゲノム」の共通項を無理やり探しました。Show notes 死がふたりを分かつまで やくしまるえつこ　わたしは人類 (YouTube) やくしまるえつこさんによる「わたしは人類」の解説 … やくしまるえつこさんによるわたしは人類の解説。ぜひ読んでいただきたい。 やくしまるえつこさんによる「わたしは人類(I’m Humanity)」の解説 … シアノバクテリアと塩基の情報があります。 Ohno and Ohno. Immunogenetics (1986) … 大野夫妻によるDNA music論文のオリジナル Susumu Ohno, DNA Music (YouTube) 空間知覚拡張のための“聞こえる化”デバイスの開発 … 未踏2015にて発表された「聞こえる化」のデバイス Genomes OnLine Database: GOLD … ここで既に読まれた、もしくは現在進行中のゲノムプロジェクトを調べることができます。 Akagi et al., Science (2014) … 柿のY染色体のゲノムシーケンシングとRNA-Seqを通して、OGIとMeGIという遺伝子を発見した論文。OGIとMeGIはパラログであり、OGIはフレームシフトなどによりタンパク質としての機能は失われ、ncRNAとして働いていると考えられる。植物において初めて性決定遺伝子が同定された。OGIによるメカニズムの詳しいメカニズムは不明と言いましたがRNAiのような仕組みが働いていると考えられているようです。 Akagi et al., PLoS genetics (2020) … 今回の柿ゲノム論文。SiMeGI(Sister of MeGI)を新たなパラログとして同定。Whole genome duplicationとgene duplicationにより、カキノキ属の性決定遺伝子であるOGIとMeGIが作られたことが推定された。 whole genome duplication … 全ゲノム重複。ゲノム全体が二倍になる。 遺伝子重複(gene duplication) … 遺伝子重複。ある遺伝子が二倍になる。 パラログとオソログ Akagi et al., Plant Cell (2018) … キウイフルーツにおける性決定遺伝子「Shy girl」を同定した論文。 Kiuchi et al., Nature (2014) … カイコにおける性決定システムとncRNAに関する論文。 Editorial notes エスパーリスナーは　未来に　攻撃を予知した！(coela) Researchat.fmは、リスナーからのお便りで出演者が勉強するpodcast番組です (soh) ミームが発現し始めているのかそれともエスパーからの投稿なのか見分けがつきません…また、植物の用語がわからずメチャクチャになってしまい申し訳ございません (tadasu)

Eukaryotic gene transcription is highly complex and regulation occurs at multiple stages. RNA Polymerase II (Pol II) is recruited to promoter regions of the DNA to initiate transcription. Shortly after initiation, Pol II exchanges initiation factors for elongation factors. After Pol II passes termination signals, the RNA is cleaved and Pol II eventually released from the DNA template. pre-mRNAs are polyadenylated and exported to the cytosol for translation and ultimately degradation. Mechanisms regulating transcription have been studied extensively, but mechanisms of mRNA degradation are less well understood. To monitor mRNA synthesis and degradation, we developed the comparative dynamic transcriptome analysis (cDTA). cDTA provides absolute rates of mRNA synthesis and decay in Saccharomyces cerevisiae Sc cells with the use of Schizosaccharomyces pombe Sp cells as internal standard. We show that Sc mutants can buffer mRNA levels and that impaired transcription causes decreased mRNA synthesis rates compensated by decreased decay rates. Conversely, impairing mRNA degradation causes decreased decay rates, but also decreased synthesis rates. Thus, although separated by the nuclear membrane, transcription and mRNA degradation are coupled. In addition to regulated mRNA synthesis, pervasive transcription can be found throughout the genome, governed by an intrinsic affinity of Pol II for DNA. These divergent noncoding RNAs (ncRNAs) stem to a large extent from bidirectional promoters. However, global mechanisms for the termination of ncRNA synthesis that could act as a transcriptome surveillance mechanism are not known. It is also unclear if such a surveillance system protects the transcriptome from deregulation. Here we show that ncRNA transcription in Sc is globally restricted by early termination which relies on the essential RNA-binding factor Nrd1. Depletion from the nucleus results in Nrd1-unterminated transcripts (NUTs) that originate from nucleosome-depleted regions (NDRs) throughout the genome and can deregulate mRNA synthesis by antisense repression and transcription interference. Transcriptome-wide Nrd1-binding maps reveal divergent NUTs at essentially all promoters and antisense NUTs in most 3’-regions of genes. Nrd1 preferentially binds RNA motifs which are enriched in ncRNAs and depleted in mRNAs except in some mRNAs whose synthesis is controlled by transcription attenuation. These results describe a mechanism for transcriptome surveillance that selectively terminates ncRNA synthesis to provide promoter directionality and prevent transcriptome deregulation

Davide Corona, University of Palermo, Palermo - Italy speaks on "Chromatin Binding, Nucleosome Spacing and ncRNA-mediated Regulation of the Remodeling ATPase ISWI". This seminar has been recorded at University of Trieste by ICGEB Trieste

Since their discovery, RNA molecules have been shown to carry functions that extend far beyond their initially ascribed role as intermediates in protein biosynthesis. These noncoding RNAs (ncRNAs) are involved in fundamental cellular processes including the regulation of gene expression and maintenance of genome stability. In most cases the biogenesis or function of the RNA molecule is only possible if the molecule folds into a characteristic two- and three-dimensional shape via formation of intra-molecular base pairs. The disruption of these paired regions through mutations in the primary sequence can result in conformational changes of the molecule that impair its ability to function correctly. However, compensatory mutations can restore the original conformation of the molecule. Under the influence of various evolutionary forces, such as mutation and selection, a paired region (helix) will accumulate these nucleotide double-substitutions (covariations). The chance of a substitution and thus the rate of evolution depends on different properties of the helix. We developed a logistic regression approach to analyze the evolutionary dynamics of RNA secondary structures (Piskol and Stephan, 2008). This method was applied to a set of computationally predicted RNA secondary structures in vertebrate introns. Our aim was to discover structural and population genetic determinants of the compensatory mutation rate in RNA molecules. As predicted by Kimura’s (1985) model of compensatory evolution, our results are in agreement with the hypothesis that the physical distance between pairing nucleotides has a negative influence on the occurrence of covariations. Furthermore, we found that longer pairing regions have the ability to tolerate more wobbles (GU base pairs) and mismatches, and ultimately also contain more covariations. The position-wise analysis of all nucleotides in paired regions revealed that covariations occur preferentially at the helix ends, whereas wobbles and mismatches are more frequent in the middle of a helix. This pattern is largely determined by the GC content. We extended the study described above from structured regions in introns of vertebrate genes to folded RNA molecules that are scattered across the whole nuclear genomes of drosophilids (Drosophila melanogaster/D. simulans) and hominids (human/chimp). For these molecules we estimated genome wide selective constraints (Piskol and Stephan, 2011). In comparison to neutrally evolving regions of the same genomes we observed substantially reduced rates of substitutions at paired and unpaired sites of folded molecules. We found that more than 90% of novel mutations in ncRNAs are removed from the sequence by purifying selection. These values exceed estimates that were previously obtained for amino-acid changing positions of protein coding genes. It points to the overall importance of many folded genomic regions, which carry quite diverse functions (correct splicing, splicing efficiency, protein localization, RNA editing). We did not find significant differences in constraints between folded molecules based on their genomic location (coding/noncoding, genic/intergenic, UTR/non-UTR). Therefore, the restricted evolution of ncRNAs seems to be mostly driven by the basic need of the molecule to remain in its original conformation through continuous maintenance of pairings between nucleotides and only to a smaller extent by the location of the molecule in the genome. In addition, a comparison of selective coefficients between drosophilids and hominids enabled us to find evidence for the impact of the effective population size on RNA evolution, which resulted in significantly higher constraints in drosophilids than hominids and led to larger differences in selective constraints at unpaired than at paired positions. Motivated by the evidence for a potential role of the effective population size in the evolution of ncRNA molecules we explored this topic in greater detail. The effective population size of a species (N_e) is a fundamental quantity in population genetics. Its impact on the efficacy of selection has been the focus of many theoretical and empirical studies over the recent years. Yet, the effect of N_e was mostly investigated in connection with the evolution of independently evolving sites in a genome, while its impact on the evolution of epistatic interactions is not well understood. Our previous work (see previous paragraph) showed evidence for the role of N_e in the evolution of ncRNA molecules (which consist to a large extent of coevolving regions). To increase our knowledge of the impact of N_e on the evolution at independently evolving and coevolving sites, we focused on transfer RNAs (tRNAs) - a class of RNA molecules with well studied structure and function. We compared the rates of evolution at paired and unpaired positions in orthologous tRNAs of various vertebrate and Drosophila species. Therefore, we chose groups of species that differ in their long-term effective population sizes and compared the level of selective constraint between them. These pairs included human/macaque, macaque/marmoset, dog/cat, chicken/zebra finch, mouse/rat, D. melanogaster/D. yakuba, and D. melanogaster/D. simulans. Indeed, we were able to detect differences in selective constraints between species pairs of different N_e. These differences can be explained well by theoretical predictions for the evolution of independently evolving and coevolving sites. Specifically, we found that constraints in orthologous tRNAs of a species pair increase with increasing long-term N_e. Thereby, the effect of N_e is stronger at unpaired(independently evolving) sites than paired (coevolving) sites. Furthermore, for all species pairs we identified sets of orthologous tRNAs with high structural similarity to tRNAs from all major kingdoms of life (’core’ sets), and tRNAs with lower similarity (’peripheral’ sets). We found the core sets to be under strong overall constraints and only subject to a negligible effect of N_e. In the peripheral set, however, we discovered a strong influence of N_e on constraints. We also investigated whether the difference in N_e between autosomes and X chromosome, due to the presence of the X chromosome in one copy in males, has an effect on differences in evolutionary rates. We were able to show that constraints are more relaxed in X-linked tRNAs.