Open AccessDissertation
G-quadruplexes and gene expression in Arabidopsis thaliana
TLDR
A novel method for identifying G4s is introduced, which uses a machine learning approach trained on datasets derived from the high throughput sequencing of G4 structures, to study the prevalence of PG4s in the genome of Arabidopsis thaliana, the model plant.Abstract:
G-Quadruplexes (G4s) are four stranded DNA structures which form in regions with high GC content and high GC skew. Because of the dependence of G4 structure on specific sequences, it is possible to predict putative G4s (PG4s) throughout genomic sequence. PG4s are non-uniformly distributed in genomes, with higher densities within various genic features, particularly promoters, 5’ untranslated regions (UTRs) and coding sequences (CDSs). When they form G4s, these sequences can have a variety of implications for biological processes including replication, transcription, translation and splicing. Here, we introduce a novel method for identifying PG4s, which uses a machine learning approach trained on datasets derived from the high throughput sequencing of G4 structures. We apply this and other techniques, to study the prevalence of PG4s in the genome of Arabidopsis thaliana, the model plant. Finally, we study the effect of G4 stabilisation on gene expression in Arabidopsis, using the GQuadruplex binding agent N-methyl mesoporphyrin (NMM). We identify a family of genes which are strongly downregulated by NMM, and find that they contain large numbers of PG4s in their CDSs.read more
Citations
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References
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Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs
Hagen Tilgner,David G. Knowles,Rory Johnson,Carrie A. Davis,Sudipto K. Chakrabortty,Sarah Djebali,Joao Curado,Michael Snyder,Thomas R. Gingeras,Roderic Guigó +9 more
TL;DR: The coSI measure, based on RNA-seq reads mapping to exon junctions and borders, is introduced, to assess the degree of splicing completion around internal exons, and significant enrichment of spliceosomal snRNAs in chromatin-associated RNA is found compared with other cellular RNA fractions and other nonspliceosome sn RNAs.
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Potent effect of target structure on microRNA function.
TL;DR: A potent effect of target structure on target recognition by miRNAs is indicated and a structure-based framework for genome-wide identification of animal miRNA targets is established.
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Re-evaluation of G-quadruplex propensity with G4Hunter
TL;DR: The G4Hunter algorithm is applied to genomes of a number of species, including humans, allowing us to conclude that the number of sequences capable of forming stable quadruplexes (at least in vitro) in the human genome is significantly higher, by a factor of 2–10, than previously thought.
Journal ArticleDOI
A Structural Model of Transcription Elongation
Nataliya Korzheva,Arkady Mustaev,Maxim Kozlov,Arun Malhotra,Vadim Nikiforov,Alex Goldfarb,Seth A. Darst +6 more
TL;DR: The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase and transcript RNA or template DNA onto the x-ray crystal structure and the resulting model provides insight into the functional properties of the transcription complex.