THE CARBOXY-TERMINAL DOMAIN (CTD) OF RNA- POLYMERASE-II PLAYS A PIVOTAL ROLE IN MESSENGER-RNA METABOLISM

RNA polymerase (RNAP) II is a multisubunit enzyme composed of several different subunits. The largest subunit shows an intriguing carboxy-te rminal domain (CTD) which consists in multiple repeats of a seven amin o-acid motif. The same motif is-repeated 26 times in the yeast protein and up to 52 times in the mammalian protein. An unphosphorylated CTD is essential for the assembly of RNA polymerase and general transcript ion factors into a preinitiation complex of transcription on promoters . Phosphorylation of the CTD by the transcription factor TFIIH is requ ired to elongate transcription, but other CTD kinases may also contrib ute to it. The CTD is also required for pre-mRNA splicing and polyaden ylation. But in this case, phosphorylation of the CTD is necessary to associate the splicing machinery. In cells, the phosphorylation status of the CTD of the largest subunit is tightly regulated by a balance b etween protein kinases and phosphatases. Environmental and development al programs influence this balance and may thus directly influence the overall mRNA metabolism.