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Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns.

ABSTRACT: The number of regulatory RNAs with identified non-canonical structures is increasing, and structural transitions often play a role in their biological function. This stimulates interest in internal motions of RNA, which can underlie structural transitions. Heteronuclear NMR relaxation measurements, which are commonly used to study internal motion, only report on local motions of few sites within the molecule. Here we have studied a 27-nt segment of the human hepatitis B virus (HBV) pregenomic RNA, which is essential for viral replication. We combined heteronuclear relaxation with the new off-resonance ROESY technique, which reports on internal motions of H,H contacts. Using off-resonance ROESY, we could for the first time detect motion of through-space H,H contacts, such as in intra-residue base-ribose contacts or inter-nucleotide contacts, both essential for NMR structure determination. Motions in non-canonical structure elements were found primarily on the sub-nanosecond timescale. Different patterns of mobility were observed among several mobile nucleotides. The most mobile nucleotides are highly conserved among different HBV strains, suggesting that their mobility patterns may be necessary for the RNA's biological function.

SUBMITTER: Petzold K

PROVIDER: S-EPMC2175316 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns.

Petzold Katja K Duchardt Elke E Flodell Sara S Larsson Göran G Kidd-Ljunggren Karin K Wijmenga Sybren S Schleucher Jürgen J

Nucleic acids research 20071011 20

The number of regulatory RNAs with identified non-canonical structures is increasing, and structural transitions often play a role in their biological function. This stimulates interest in internal motions of RNA, which can underlie structural transitions. Heteronuclear NMR relaxation measurements, which are commonly used to study internal motion, only report on local motions of few sites within the molecule. Here we have studied a 27-nt segment of the human hepatitis B virus (HBV) pregenomic RN ...[more]

PMID: 17933777

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Project description:The clinical spectrum of Alzheimer's disease (AD) extends well beyond the classic amnestic-predominant syndrome. The previous studies have suggested differential neurofibrillary tangle (NFT) burden between amnestic and logopenic primary progressive aphasia presentations of AD. In this study, we explored the regional distribution of NFT pathology and its relationship to AD presentation across five different clinical syndromes. We assessed NFT density throughout six selected neocortical and hippocampal regions using thioflavin-S fluorescent microscopy in a well-characterized clinicopathological cohort of pure AD cases enriched for atypical clinical presentations. Subjects underwent apolipoprotein E genotyping and neuropsychological testing. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z score. Our results showed that NFT regional burden aligns with the clinical presentation and region-specific cognitive scores. Cortical, but not hippocampal, NFT burden was higher among atypical clinical variants relative to the amnestic syndrome. In analyses of specific clinical variants, logopenic primary progressive aphasia showed higher NFT density in the superior temporal gyrus (p = 0.0091), and corticobasal syndrome showed higher NFT density in the primary motor cortex (p = 0.0205) relative to the amnestic syndrome. Higher NFT burden in the angular gyrus and CA1 sector of the hippocampus were independently associated with worsening visuospatial dysfunction. In addition, unbiased hierarchical clustering based on regional NFT densities identified three groups characterized by a low overall NFT burden, high overall burden, and cortical-predominant burden, respectively, which were found to differ in sex ratio, age, disease duration, and clinical presentation. In comparison, the typical, hippocampal sparing, and limbic-predominant subtypes derived from a previously proposed algorithm did not reproduce the same degree of clinical relevance in this sample. Overall, our results suggest domain-specific functional consequences of regional NFT accumulation. Mapping these consequences presents an opportunity to increase understanding of the neuropathological framework underlying atypical clinical manifestations.

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Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns.

Publications

Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns.

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