Gene expression in higher eukaryotes is a complicated, multistep process. One feature which distinguishes this process from that occurring in prokaryotes is the extensive series of post transcriptional events which culminate in transport of mature messenger RNA out of neclei. One of these modifications is splicing - the removal of intervening RNA sequences from long initial transcripts with concomitant ligation of conserved RNA sequences. Recently is has been suggested that a class of ubiquitous small nuclear ribonucleoproteins may be involved in splicing and perhaps part of the actual splicing catalytic factor. This proposal centers on studying these ribonucleoproteins and several other closely related ones probably also involved in RNA biosynthesis. Very little is known about these macromolecular assemblies and the experiments described herein are designed to investigate their biochemical structure and molecular function. In a chronological sense the proposed research will involve the purification, physical characterization (constituent identification, topographical distribution and biochemical properties), in vitro assembly, and determination of function of these ribonucleoproteins. The immediate objective is to understand how these ribonucleoproteins are involved in mRNA synthesis, modification and/or transport in an attempt to approach the long-term objective of the molecular description of eukaryotic transcription and its control. We know very little about the control of transcription in eukaryotes and the role it may play in developmental, normal or abnormal processes. The ribonucleoproteins described above are particular to higher eukaryotes as is the transcriptional step in which they participate. The understanding of gene expression in eukaryotes and its ramifications in terms of disease or abnormal states will ultimately depend on understanding the molecular basis by which such expression occurs.
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