261 research outputs found
Protein-RNA interactions: a structural analysis
No full textA detailed computational analysis of 32 protein-RNA complexes is presented. A number of physical and chemical properties of the intermolecular interfaces are calculated and compared with those observed in protein-double-stranded DNA and protein-single-stranded DNA complexes. The interface properties of the protein-RNA complexes reveal the diverse nature of the binding sites. van der Waals contacts played a more prevalent role than hydrogen bond contacts, and preferential binding to guanine and uracil was observed. The positively charged residue, arginine, and the single aromatic residues, phenylalanine and tyrosine, all played key roles in the RNA binding sites. A comparison between protein-RNA and protein-DNA complexes showed that whilst base and backbone contacts (both hydrogen bonding and van der Waals) were observed with equal frequency in the protein-RNA complexes, backbone contacts were more dominant in the protein-DNA complexes. Although similar modes of secondary structure interactions have been observed in RNA and DNA binding proteins, the current analysis emphasises the differences that exist between the two types of nucleic acid binding protein at the atomic contact level
Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome
No full textNucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable (‘strong’) nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when subject to increased mutation rates, transposons are then more rapidly inactivated. Depletion of strong nucleosomes in older transposons suggests frequent positioning changes during evolution. The findings have important implications for human genetics and genome evolution
Near Field Scanning Optical Microscopy(NSOM) of nano devices
No full textThis thesis aims to investigate the optical properties of nano-devices using the technique of Near-Field Scanning Optical Microscopy (NSOM). A unique setup to perform Atomic Force Microscopy (AFM) and NSOM simultaneously in a scanning electron microscope (SEM) to collect spatially resolved luminescence and image transport on nano-scale structures, particularly nanowires, will allow direct determination of transport parameters, such as minority carrier mobility and diffusion length that are vital to the performance of optoelectronic devices. The work involves the development of a unique nano-scale imaging technique applicable to a wide range of structures. The main structures of interest in this thesis will be GaN nanowires. Instead of using a laser for generating charge for imaging, the e-beam from the SEM was used to generate localized charge for an NSOM probe to monitor the motion of the excess charge due to diffusion and/or drift via electron-hole recombination process. For the first time in this research, the author addressed numerous challenges such as the intricate NSOM technique to resolve sub-wavelength dimension measurements of the elements and determine optimized experimental parameters to compensate for the relatively low efficiency of NSOM optical collection. Of significance, transport imaging of 1-10 [micrometer] long GaN nanowires resulted in minority carrier diffusion lengths ranging from 1-2 [micrometer]. An initial experimental exploration was also conducted to determine the theoretical prediction of the unique transmission enhancement of Au nanobowties fabricated on luminescent GaAs heterostructure. The author will report the working principles, experimental procedures, optimal process parameters and the respective imaging results for assessing the properties of the nano-devices studied in this thesis work. Recommendations for future work pertaining to the augmentation of related NSOM work will also be made to ensure continued progress in this area of work.Approved for public release; distribution is unlimited.Singapore Armed Forces author.http://archive.org/details/nearfieldscannin10945374
How Do You Identify m⁶A Methylation in Transcriptomes at High Resolution? A Comparison of Recent Datasets
No full textIntegrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome
No full textUnderstanding the molecular mechanisms and evolution of the gene regulatory system remains a major challenge in biology. Transcription start sites (TSSs) are especially interesting because they are central to initiating gene expression. Previous studies revealed widespread transcription initiation and fast turnover of TSSs in mammalian genomes. Yet, how new TSSs originate and how they evolve over time remain poorly understood. To address these questions, we analyzed ∼200,000 human TSSs by integrating evolutionary (inter- and intra-species) and functional genomic data, particularly focusing on evolutionarily young TSSs that emerged in the primate lineage. TSSs were grouped according to their evolutionary age using sequence alignment information as a proxy. Comparisons of young and old TSSs revealed that (1) new TSSs emerge through a combination of intrinsic factors, like the sequence properties of transposable elements and tandem repeats, and extrinsic factors such as their proximity to existing regulatory modules; (2) new TSSs undergo rapid evolution that reduces the inherent instability of repeat sequences associated with a high propensity of TSS emergence; and (3) once established, the transcriptional competence of surviving TSSs is gradually enhanced, with evolutionary changes subject to temporal (fewer regulatory changes in younger TSSs) and spatial constraints (fewer regulatory changes in more isolated TSSs). These findings advance our understanding of how regulatory innovations arise in the genome throughout evolution and highlight the genomic robustness and evolvability in these processes
Computational approaches to study transcriptional regulation in the human genome
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 22-02-200
Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome.
No full textNucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable ('strong') nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when subject to increased mutation rates, transposons are then more rapidly inactivated. Depletion of strong nucleosomes in older transposons suggests frequent positioning changes during evolution. The findings have important implications for human genetics and genome evolution
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