Regulatory Mechanisms Controlling Alternative Splicing

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The human genome possesses ~21000 genes; genes encode proteins, but the genes themselves are split, organizing the protein coding regions into discrete blocks called "exons". In each cell only a subset of genes are transcribed into RNA in a process called "transcription". The RNAs are then used to guide the production of proteins of the prescribed sequence. After the genes are transcribed into RNA the exons are stitched together in a process called "splicing". The splicing process can also stitch the exons together in alternative orders which will generate proteins with different sequences and functions. The unique set of proteins within a cell is defined by control processes that regulate transcription and splicing to select which genes and which order of the exons are used. This regulation is a primary means cells modify their protein repertoire to adapt to their environment. Recently, scientists have learned that splicing and transcription are not regulated independently, but are co-regulated by proteins and processes not yet understood. We study two closely related human proteins that may regulate both the order of exons and modulate the level of transcription. These proteins are enzymes, called "kinases", which add a phosphate molecule to sites on other proteins, thus modifying their function. In our experiments we have identified several other proteins that interact with these kinases, thus providing information on how these kinases carry out their functions. In our studies we will characterize the specific functions of both kinases and their interacting proteins. From this information we will learn more about how the process that controls the order of exon splicing is coordinated with the activity of the process that transcribes genes into RNA. This will help us understand, and perhaps control, how cells express a unique set of genes to live and grow.