Divergence of exonic splicing elements after gene duplication and the impact on gene structures

An analysis of human exonic splicing elements in duplicated genes reveals their important role in the generation of new gene structures

Evidence for common short natural trans sense-antisense pairing between transcripts from protein coding genes

A computational prediction of human coding RNA trans short sense-antisense pairs suggests that mRNA regulation by other coding transcripts might be a common occurrence

Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay

<p>Abstract</p> <p>Background</p> <p>Nonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed.</p> <p>Results</p> <p>To resolve this issue we examined the properties of putative nonsense-mediated decay targets in humans and mice. We started with a well-annotated set of protein coding genes and found that 2 to 4% of genes are probably subject to nonsense-mediated decay, and that the premature termination codon reflects neither rare mutations nor sequencing artefacts. Several lines of evidence suggested that the noisy splicing model has considerable relevance: 1) exons that are uniquely found in nonsense-mediated decay transcripts (nonsense-mediated decay-specific exons) tend to be newly created; 2) have low-inclusion level; 3) tend not to be a multiple of three long; 4) belong to genes with multiple splice isoforms more often than expected; and 5) these genes are not obviously enriched for any functional class nor conserved as nonsense-mediated decay candidates in other species. However, nonsense-mediated decay-specific exons for which distant orthologous exons can be found tend to have been under purifying selection, consistent with the regulation model.</p> <p>Conclusion</p> <p>We conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.</p

Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals

Comparison of gene expression variation in autosomal and X-linked genes reveals that high transcriptional noise is not a necessary consequence of haploid expression

Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features

Background: Study of drug-target interaction networks is an important topic for drug development. It is both timeconsuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. Methods/Principal Findings: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. Conclusion/Significance: Our results indicate that the network prediction system thus established is quite promising an

Removal of Hsf4 leads to cataract development in mice through down-regulation of γS-crystallin and Bfsp expression

<p>Abstract</p> <p>Background</p> <p>Heat-shock transcription factor 4 (HSF4) mutations are associated with autosomal dominant lamellar cataract and Marner cataract. Disruptions of the <it>Hsf4 </it>gene cause lens defects in mice, indicating a requirement for HSF4 in fiber cell differentiation during lens development. However, neither the relationship between HSF4 and crystallins nor the detailed mechanism of maintenance of lens transparency by HSF4 is fully understood.</p> <p>Results</p> <p>In an attempt to determine how the underlying biomedical and physiological mechanisms resulting from loss of HSF4 contribute to cataract formation, we generated an <it>Hsf4 </it>knockout mouse model. We showed that the <it>Hsf4 </it>knockout mouse (<it>Hsf4</it>^-/-) partially mimics the human cataract caused by HSF4 mutations. Q-PCR analysis revealed down-regulation of several cataract-relevant genes, including <it>γS-crystallin (Crygs) </it>and lens-specific beaded filament proteins 1 and 2 (<it>Bfsp1 </it>and <it>Bfsp2</it>), in the lens of the <it>Hsf4</it>^-/-mouse. Transcription activity analysis using the dual-luciferase system suggested that these cataract-relevant genes are the direct downstream targets of HSF4. The effect of HSF4 on <it>γS-crystallin </it>is exemplified by the cataractogenesis seen in the <it>Hsf4</it>^-/-,<it>rncat </it>intercross. The 2D electrophoretic analysis of whole-lens lysates revealed a different expression pattern in 8-week-old <it>Hsf4</it>^-/-mice compared with their wild-type counterparts, including the loss of some αA-crystallin modifications and reduced expression of γ-crystallin proteins.</p> <p>Conclusion</p> <p>Our results indicate that HSF4 is sufficiently important to lens development and disruption of the <it>Hsf4 </it>gene leads to cataracts via at least three pathways: 1) down-regulation of <it>γ-crystallin</it>, particularly <it>γS-crystallin</it>; 2) decreased lens beaded filament expression; and 3) loss of post-translational modification of αA-crystallin.</p