title: TATA boxes in gene transcription and poly (A) tails in mRNA stability: New perspective on the effects of berberine.
abstract: Berberine (BBR) is a natural compound with variable pharmacological effects and a broad panel of target genes. We investigated berberine's pharmacological activities from the perspective of its nucleotide-binding ability and discovered that BBR directly regulates gene expression by targeting TATA boxes in transcriptional regulatory regions as well as the poly adenine (poly (A)) tail at the mRNA terminus. BBR inhibits gene transcription by binding the TATA boxes in the transcriptional regulatory region, but it promotes higher levels of expression by targeting the poly (A) tails of mRNAs. The present study demonstrates that TATA boxes and poly (A) tails are the first and second primary targets by which BBR regulates gene expression. The final outcome of gene regulation by BBR depends on the structure of the individual gene. This is the first study to reveal that TATA boxes and poly (A) tails are direct targets for BBR in its regulation of gene expression. Our findings provide a novel explanation for the complex activities of a small molecule compound in a biological system and a novel horizon for small molecule-compound pharmacological studies.
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi-Yi
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Lei
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yu-Shuang
authors.initials: YS
authors.lastname: Chai
authors.affiliation: MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Jiang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Tian-Shi
authors.initials: TS
authors.lastname: Feng
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xin-Pei
authors.initials: XP
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Yan
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Xing
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Du
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001599:Berberine / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011061:Poly A; D020871:RNA Stability / Q000187:drug effects*; D016385:TATA Box; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D020413:3' Untranslated Regions; D001599:Berberine; D011061:Poly A