C-terminus

Abstract: The C-terminal repeat domain (CTD), an unusual extension appended to the C terminus of the largest subunit of RNA polymerase II, serves as a flexible binding scaffold for numerous nuclear factors; which factors bind is determined by the phosphorylation patterns on the CTD repeats. Changes in phosphorylation patterns, as polymerase transcribes a gene, are thought to orchestrate the association of different sets of factors with the transcriptase and strongly influence functional organization of the nucleus. In this review we appraise what is known, and what is not known, about patterns of phosphorylation on the CTD of RNA polymerases II at the beginning, the middle, and the end of genes; the proposal that doubly phosphorylated repeats are present on elongating polymerase is explored. We discuss briefly proteins known to associate with the phosphorylated CTD at the beginning and ends of genes; we explore in more detail proteins that are recruited to the body of genes, the diversity of their functions, and the potential consequences of tethering these functions to elongating RNA polymerase II. We also discuss accumulating structural information on phosphoCTD-binding proteins and how it illustrates the variety of binding domains and interaction modes, emphasizing the structural flexibility of the CTD. We end with a number of open questions that highlight the extent of what remains to be learned about the phosphorylation and functions of the CTD.

Abstract: The Harvey murine sarcoma virus (Ha-MuSV) transforming gene, v-rasH, encodes a 21,000 molecular weight protein (p21) that is closely related to the p21 proteins encoded by the cellular transforming genes of the ras gene family1–8 The primary translation product (prop21), which is found in the cytosol, undergoes post-translational modification9 and the mature protein subsequently becomes associated with the inner surface of the plasma membrane and binds lipid tightly10,11 The p21 proteins have the capacity to bind guanine nucleotides non-covalently in vitro3,12 To assess the biological relevance of these biochemical features of the protein, we have now studied a series of deletion mutants located at or near the C-terminus of the viral p21 protein Our tissue culture studies indicate that amino acids located at or near the C-terminus are required for cellular transformation, membrane association and lipid binding