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Combinatorial post‐translational modifications of RNA polymerase II
Author(s) -
Lothrop Adam,
Kulla Daniel,
Lin YuShan,
Fuchs Stephen
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.555.5
Subject(s) - ctd , rna polymerase ii , transcription (linguistics) , phosphorylation , pin1 , chemistry , computational biology , messenger rna , microbiology and biotechnology , biology , biochemistry , gene , gene expression , isomerase , promoter , oceanography , linguistics , philosophy , geology
RNA polymerase II (RNAP II) is responsible for transcription of the majority of mRNA in eukaryotes. The C‐terminal domain (CTD) of RNAP II contains multiple types of post‐translational modifications (PTMs), which facilitates the interactions between a large number of transcriptionally‐associated factors and the CTD itself. Temporal regulation of these binding events is orchestrated by a dynamic arrangement of PTMs. The prolyl isomerase Pin1 impacts the CTD phosphorylation state, demonstrating cross‐talk between these two types of PTMs. To investigate the relationship between these modifications, we have constructed a library of CTD peptides containing varying combinations of phosphoserine and a proline analog that is biased towards the cis conformation. With the noted importance of CTD phosphorylation, we used these peptides in array based assays to determine the effects of proline isomerization on CTD kinase activity. Assay data is combined with a computational approach, utilizing molecular dynamics simulations to investigate PTM effects on CTD conformation. The data from this study provides a detailed portrait of the complex interplay of PTMs in regulating important interactions of the CTD with other protein factors during transcription. Supported by Tufts University startup funding to S.M.F.