Mar 08, 2011 13:05
Hey, all you smart people on my friends list who have PhD's -- could you send me copies of your dissertation abstracts? I need some templates to look at, and it's more fun to ask for yours than to on the University's Library website. :)
academia,
query,
writing
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Nature has evolved many mechanisms to control gene expression, including post-transcriptional regulation by alternative mRNA splicing. Alternative splicing can regulate gene expression by processing transcripts into forms that are degraded rather than translated into protein. In this process, known as unproductive splicing, the resulting mRNAs contain premature stop codons and are thus removed by nonsense-mediated mRNA decay (NMD). We investigated examples of unproductive splicing in human genes and found that, strikingly, all human SR splicing factors were alternatively spliced into mRNAs that were targets of NMD. Alternative splicing of the SR genes was associated with ultraconserved genomic elements, regions of the human genome that are exactly conserved in rodent genomes. This discovery illuminated a role for ultraconserved elements in post-transcriptional regulation. We studied the evolution of unproductive splicing and ultraconserved elements in SRp40, SRp55, and SRp75, a closely related subgroup within the SR family. Orthologs of this subgroup originated through a series of duplications and gene losses within the deuterostomes. The unproductive splicing and ultraconservation in SRp55 and SRp75 originated in vertebrates, but the unproductive splicing of SRp40 is ancient, originating before the divergence of deuterostomes and insects. The impact of unproductive splicing on expression in Drosophila has not been established. We identified alternatively-spliced targets of NMD in fly and inferred characteristics of these mRNAs that might lead to their recognition and degradation by NMD. Unproductive splicing affects diverse targets, but in a subset of these targets, a common theme has emerged: genes encoding splicing factors employ unproductive splicing to regulate their expression, and this regulation is associated with some of the most conserved regions of the human genome.
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