title: Acetylation-Dependent Control of Global Poly(A) RNA Degradation by CBP/p300 and HDAC1/2.
abstract: Acetylation of histones and transcription-related factors is known to exert epigenetic and transcriptional control of gene expression. Here we report that histone acetyltransferases (HATs) and histone deacetylases (HDACs) also regulate gene expression at the posttranscriptional level by controlling poly(A) RNA stability. Inhibition of HDAC1 and HDAC2 induces massive and widespread degradation of normally stable poly(A) RNA in mammalian and Drosophila cells. Acetylation-induced RNA decay depends on the HATs p300 and CBP, which acetylate the exoribonuclease CAF1a, a catalytic subunit of the CCR4-CAF1-NOT deadenlyase complex and thereby contribute to accelerating poly(A) RNA degradation. Taking adipocyte differentiation as a model, we observe global stabilization of poly(A) RNA during differentiation, concomitant with loss of CBP/p300 expression. Our study uncovers reversible acetylation as a fundamental switch by which HATs and HDACs control the overall turnover of poly(A) RNA.
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Poetz
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Bruer
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Thi Bach Nga
authors.initials: TB
authors.lastname: Ly-Hartig
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schott
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67404 Illkirch, France; Centre National de Recherche Scientifique (CNRS) UMR 7104, 67404 Illkirch, France; INSERM U964, 67404 Illkirch, France; Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
authors.affiliation: Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. Electronic address: georg.stoecklin@medma.uni-heidelberg.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Stoecklin
mesh_terms: D041721:3T3-L1 Cells; D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D011061:Poly A / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D011061:Poly A; D012333:RNA, Messenger; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C489780:CNOT8 protein, human; C539882:NR4A2 protein, human; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human