Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing

Tadahiro Shimazu; Sueharu Horinouchi; Minoru Yoshida

doi:10.1074/jbc.M609745200

Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing

J Biol Chem. 2007 Feb 16;282(7):4470-4478. doi: 10.1074/jbc.M609745200. Epub 2006 Dec 17.

Authors

Tadahiro Shimazu¹, Sueharu Horinouchi², Minoru Yoshida³

Affiliations

¹ Chemical Genetics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198, Japan; Department of Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan, and.
² Department of Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan, and.
³ Chemical Genetics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198, Japan; Department of Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan, and; CREST Research Project, JST, Saitama 332-0012, Japan. Electronic address: yoshidam@riken.jp.

PMID: 17172643
DOI: 10.1074/jbc.M609745200

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / metabolism*
Acetylation / drug effects
Animals
COS Cells
CREB-Binding Protein / metabolism*
Chlorocebus aethiops
Enzyme Inhibitors / pharmacology
Histone Deacetylase Inhibitors*
Histone Deacetylases / metabolism*
Humans
Hydroxamic Acids / pharmacology
Polynucleotide Adenylyltransferase / metabolism
Protein Binding / drug effects
Protein Processing, Post-Translational / drug effects
RNA Precursors / metabolism*
RNA Processing, Post-Transcriptional / drug effects
RNA Processing, Post-Transcriptional / physiology*
Sirtuin 1
Sirtuin 2
Sirtuins / metabolism
Tubulin / metabolism
Tumor Suppressor Protein p53 / metabolism
alpha Karyopherins / metabolism
beta Karyopherins
mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

3' Untranslated Regions
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Hydroxamic Acids
RNA Precursors
Tubulin
Tumor Suppressor Protein p53
alpha Karyopherins
beta Karyopherins
cleavage factor Im, human
mRNA Cleavage and Polyadenylation Factors
trichostatin A
CREB-Binding Protein
CREBBP protein, human
Polynucleotide Adenylyltransferase
SIRT1 protein, human
SIRT2 protein, human
Sirtuin 1
Sirtuin 2
Sirtuins
Histone Deacetylases