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Posttranscriptional Regulation of Human ADH5/FDH and Myf6 Gene Expression by Upstream AUG Codons

Authors
 Hye-Sook Kwon  ;  Dong-Kee Lee  ;  Jae-Jung Lee  ;  Howard J. Edenberg  ;  Yong-ho Ahn  ;  Man-Wook Hur 
Citation
 ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, Vol.386(2) : 163-171, 2001 
Journal Title
 ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 
ISSN
 0003-9861 
Issue Date
2001
MeSH
3T3 Cells ; 5' Untranslated Regions/genetics ; Aldehyde Oxidoreductases/biosynthesis ; Aldehyde Oxidoreductases/genetics* ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Codon, Initiator/genetics* ; Down-Regulation ; Gene Expression Regulation* ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Mutation/genetics ; Myogenic Regulatory Factors/biosynthesis ; Myogenic Regulatory Factors/genetics* ; Nucleic Acid Conformation ; Open Reading Frames/genetics* ; Protein Biosynthesis/genetics* ; RNA, Messenger/chemistry ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ribosomes/metabolism ; Tandem Repeat Sequences/genetics ; Transcription, Genetic/genetics
Abstract
Upstream open-reading frames are unusual in mammalian mRNAs. The 5′ untranslated region of ADH5 mRNA contains an upstream open-reading frame (uORF) with two possible AUG start codons. Myf6 mRNA contains three tandem AUG repeats at the translation start site, a rare feature. Mutation at one or both of the upstream AUG codons in the ADH5 mRNA increased gene expression twofold in CV-1, NIH/3T3, HeLa, and SL2 cells. Mutation of these AUG codons led to 3- to 5-fold increases in activity as measured by in vitro translation assays using capped mRNAs.RNA toeprint analysis demonstrated many stalled ribosomes flanking the AUG codons and secondary structures near the AUGs. Secondary structures may increase the ability of ribosomes to recognize the two AUGs, despite their poor initiation context. The degree of repression by uAUGs varied significantly depending on the cell lines tested, which may partly explain the differential tissue expression. Myf6 is a critical myogenic transcription factor with the striking feature of three tandem AUG codons at the translation initiation site. This structure reduced expression; removing two of these AUGs led to a doubling of activity in CV-1, HeLa, and NIH/3T3 cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S0003986100922057
DOI
10.1006/abbi.2000.2205
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142404
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