Publications by authors named "Gadareth Higgs"

Structured noncoding RNAs (ncRNAs) contribute to many important cellular processes involving chemical catalysis, molecular recognition and gene regulation. Few ncRNA classes are broadly distributed among organisms from all three domains of life, but the list of rarer classes that exhibit surprisingly diverse functions is growing. We previously developed a computational pipeline that enables the near-comprehensive identification of structured ncRNAs expressed from individual bacterial genomes.

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Riboswitch architectures that involve the binding of a single ligand to a single RNA aptamer domain result in ordinary dose-response curves that require approximately a 100-fold change in ligand concentration to cover nearly the full dynamic range for gene regulation. However, by using multiple riboswitches or aptamer domains in tandem, these ligand-sensing structures can produce additional, complex gene control outcomes. In the current study, we have computationally searched for tandem riboswitch architectures in bacteria to provide a more complete understanding of the diverse biological and biochemical functions of gene control elements that are made exclusively of RNA.

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Comparative sequence analysis methods are highly effective for uncovering novel classes of structured noncoding RNAs (ncRNAs) from bacterial genomic DNA sequence datasets. Previously, we developed a computational pipeline to more comprehensively identify structured ncRNA representatives from individual bacterial genomes. This search process exploits the fact that genomic regions serving as templates for the transcription of structured RNAs tend to be present in longer than average noncoding 'intergenic regions' (IGRs) that are enriched in G and C nucleotides compared to the remainder of the genome.

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A bacterial noncoding RNA motif almost exclusively associated with genes was uncovered using comparative sequence analysis. Some PnuC proteins are known to transport nicotinamide riboside (NR), which is a component of the ubiquitous and abundant enzyme cofactor nicotinamide adenine dinucleotide (NAD). Thus, we speculated that the newly found " motif" RNAs might function as aptamers for a novel class of NAD-sensing riboswitches.

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Background: Structured noncoding RNAs (ncRNAs) play essential roles in many biological processes such as gene regulation, signaling, RNA processing, and protein synthesis. Among the most common groups of ncRNAs in bacteria are riboswitches. These cis-regulatory, metabolite-binding RNAs are present in many species where they regulate various metabolic and signaling pathways.

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The microRNA miR-155 is prominent in cancer biology. Among microRNAs that have been linked to cancer, it is the most commonly overexpressed in malignancies (PNAS 109:20047-20052, 2012). Since its discovery, miR-155 has been implicated in promoting cancers of the breast, lung, liver, and lymphatic system.

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