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A histone tail: Pre-messenger RNA splicing and the coordinated control of gene expression

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Pre-messenger RNA splicing, the removal of noncoding intron sequences from RNA , is a crucial and tightly regulated step in gene expression. This reaction is carried out by a highly-conserved, dynamic ribonucleoprotein complex, the spliceosome. Although assembly of this macromolecular machine onto a pre-messenger RNA can be observed in vitro as a biochemically isolated reaction, recent work from our lab has shown that spliceosome assembly occurs co-transcriptionally, while the nascent RNA is being synthesized, which has important mechanistic consequences. We demonstrate that histone modification mediates co-transcriptional association of the spliceosome onto RNA , and the dynamic rearrangements required for accurate splice site recognition are influenced by the state of the chromatin. Understanding these exquisitely coordinated molecular events has important biological implications, as regulation of pre-mRNA splicing is crucial for cellular response to environmental perturbations.

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