Identifying proteins that coordinate RNA synthesis with splicing: effects of a esa1-254 point mutation on splicing in yeast

Abstract

The ability for the eukaryotic cell to maintain homeostasis depends significantly on the cell’s adaptability to changes in surrounding environments. In order to maintain an internal balance, protein synthesis is highly regulated and monitored through feedback mechanisms. More specifically, transcriptional modifications such as histone acetylation and splicing allow for such a balance. DNA, partially negative tightly packs around positive histones. Chromatin modification enzymes, such as HATs and HDACs, allow for loosening and packing of chromatin. HATs loosen chromatin, allowing for RNA polymerase to bind to the DNA and enable transcription. The NuA4 HAT complex is involved in epigenetic activation of genes through its role in acetylating nucleosomal histones, enabling transcription. Esa1, the catalytic subunit, plays essential roles in cell cycle progression and gene activation. Splicing is one of the modifications pre-mRNA undergoes before exiting the nucleus, a process in which intronic sequences are removed from the pre-mRNA transcript. Splicing occurs co-transcriptionally and is a reaction catalyzed by the spliceosome. The spliceosome is a complex consisting of subunits known as small nuclear ribonucleoproteins (snRNPs), a combination of unmodified pre-mRNA and associated proteins specific to each snRNP. Hypothesis for this study is that NuA4 coordinates with splicing proteins to regulate splicing.