title: Translation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon.
abstract: In the present study we investigate the impact of highly stable coding region secondary structures on mRNA translation efficiency. By introducing antisense segments into the 3'non-translated region of human alpha-globin mRNA we are able to synthesize a series of transcripts in which site-specific secondary structures are introduced without altering the primary structure of the 5' non-translated region, the coding region, or the encoded protein product. Coding region duplexes in close proximity to the AUG initiation codon are found to inhibit translation severely to a degree equal to that of a duplex that extends into the 5' non-translated region. In contrast, mRNAs containing duplexes positioned further 3' in the coding region translate at levels that are significantly higher although are still below those of native alpha-globin mRNA. The primary determinant of translation inhibition by coding region duplexes appears to be the proximity of the duplex to the AUG initiation codon and reflects a parallel inhibition of monosome formation. These data demonstrate that extensive coding region secondary structures suppress translation to a minimal or to a substantial degree depending on their distance from the initiation codon.
authors.affiliation: Howard Hughes Medical Institute, Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia 19104-6145.
authors.forename: S A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: F
authors.initials: F
authors.lastname: Cash
authors.forename: S S
authors.initials: SS
authors.lastname: Eshleman
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D003062:Codon / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D015183:Restriction Mapping; D012260:Ribonucleases; D013489:Suppression, Genetic; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D005914:Globins; D004247:DNA; D012260:Ribonucleases