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| I am a third year graduate student in the BBS program at Harvard Med School. I am interested in the system-wide dynamics of RNAs. My work is focused on mRNA splicing, which is the chief source of transcript and proteomic diversity in complex organisms due to the alternative use of exons. I have used ChIP-chip methodology to analyze genome-wide co-transcriptional regulation of mRNA splicing in yeast. These studies yielded a number of mechanistic insights, leading to our model that a subset of early splicing factors sample nascent mRNAs and are retained by RNA-dependent interactions at intron-containing genes to facilitate efficient spliceosome assembly on the appropriate transcripts. Moreover, we observed that the spliceosome was excluded from a subset of intron-containing genes enriched for developmentally regulated loci. We demonstrated novel regulated splicing of the corresponding transcripts, establishing differential recruitment of the spliceosome during transcription as a splicing regulatory mechanism.
| | Michael is a Postdoctoral Fellow at the Rockefeller University. |
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| As far as we are aware, we are the first to predict specific patterns of mRNA splicing on the basis of genome localization methods. Currently, I am exploring methods to gain similar insights in mammalians cells. Since the exon/intron structure of mammalian genes is so much more complex than in yeast, attempts to predict mRNA processing patterns on the basis of ChIP-chip data has proven technically and computationally challenging. Thus, I am developing means to identify RNAs associated with developmentally regulated RNA-binding proteins in an effort to determine the targets of specific splicing factors in disease and differentiation.
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| Finally, I am developing methods to screen for regulators of disease-related splicing events in human cells by drawing upon siRNA libraries and cDNA collections that are available through the ICCB. Overall, he hope that our genome-scale approaches will start to answer questions concerning the global regulation of mRNA splicing in mammalian cells, which has overarching importance for organismal complexity, development, and disease.
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Latest revision as of 13:31, 19 December 2010
Michael is a Postdoctoral Fellow at the Rockefeller University.
