The role of the pol II CTD in expression of human snRNA genes . (360G-Wellcome-088542_Z_09_Z)

The mammalian genes for the U1 and U2 spliceosomal snRNAs provide ideal model systems to study fundamental mechanisms underlying expression of pol II-transcribed genes. These short genes are structurally distinct from protein coding genes and ubiquitously expressed at high levels. As in expression of protein coding genes, the heptapeptide repeats comprising the CTD of the large subunit of pol II undergo dynamic phosphorylation during the transcription cycle. We have recently shown that phosphory lation of the serine in position 7 of the CTD heptapeptide (Ser7) functions as an snRNA gene-specific signal to recruit the gene-specific Integrator complex. This advance paves the way for a more detailed analysis of the role of dynamic CTD phosphorylation in expression of this major class of pol II-transcribed genes. The key goals of the proposed research are to identify the enzymes responsible for dynamic phosphorylation of the dephosphorylation of the CTD during transcription of snRNA genes and to dissect the molecular interactions critical for the snRNA gene-type-specific functions of the pol II CTD phosphorylation.