Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing.
Trichostatin A (TSA), a specific inhibitor of histone deacetylases (HDACs), induces acetylation of various non-histone proteins such as p53 and alpha-tubulin. We purified several acetylated proteins by the affinity to an anti-acetylated lysine (AcLys) antibody from cells treated with TSA and identified them by mass spectrometry. Here we report on ... acetylation of CFIm25, a component of mammalian cleavage factor Im (CF Im), and poly(A) polymerase (PAP), a polyadenylating enzyme for the pre-mRNA 3'-end. The residues acetylated in these proteins were mapped onto the regions required for interaction with each other. Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation. Acetylation of the CFIm25 occurred depending on the cleavage factor complex formation. Importantly, the interaction between PAP and CF Im complex was decreased by acetylation. We also demonstrated that acetylation of PAP inhibited the nuclear localization of PAP by inhibiting the binding to the importin alpha/beta complex. These results suggest that CBP and HDACs regulate the 3'-end processing machinery and modulate the localization of PAP through the acetylation and deacetylation cycle.
Mesh Terms:
3' Untranslated Regions, Acetylation, Animals, COS Cells, CREB-Binding Protein, Cercopithecus aethiops, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Polynucleotide Adenylyltransferase, Protein Binding, Protein Processing, Post-Translational, RNA Precursors, RNA Processing, Post-Transcriptional, Sirtuin 1, Sirtuin 2, Sirtuins, Tubulin, Tumor Suppressor Protein p53, alpha Karyopherins, beta Karyopherins, mRNA Cleavage and Polyadenylation Factors
3' Untranslated Regions, Acetylation, Animals, COS Cells, CREB-Binding Protein, Cercopithecus aethiops, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Polynucleotide Adenylyltransferase, Protein Binding, Protein Processing, Post-Translational, RNA Precursors, RNA Processing, Post-Transcriptional, Sirtuin 1, Sirtuin 2, Sirtuins, Tubulin, Tumor Suppressor Protein p53, alpha Karyopherins, beta Karyopherins, mRNA Cleavage and Polyadenylation Factors
J. Biol. Chem.
Date: Feb. 16, 2007
PubMed ID: 17172643
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