Translation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon

doi:10.1016/0022-2836(92)90619-U

Journal of Molecular Biology

Volume 226, Issue 3, 5 August 1992, Pages 609-621

https://doi.org/10.1016/0022-2836(92)90619-U Get rights and content

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 α-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 α-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.

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Citation Excerpt :
It has also been shown that some mRNAs contain in the coding region secondary structures that lead to “ribosomal pause” (36). Liebhaber et al. (37) have shown that extensive secondary structures in the coding region suppresses translation to a minimal or to a substantial degree depending on the distance of these structures from the initiation codon. Coding region duplexes in close proximity to the AUG dramatically suppress translation, whereas duplexes further downstream in the coding region have a milder effect on protein synthesis.
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^‡: Present address: Department of Pathology. University of Pennsylvania School of Medicine. Philadelphia, PA 19104. U.S.A.

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Journal of Molecular Biology

ArticleTranslation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon

Abstract

Cell

Cell

Biochem. Biophys. Res. Commun

Cell

Gene

Cell

Cell

J. Biol. Chem

J. Biol. Chem

Cell

J. Biol. Chem

J. Biol. Chem

Cell

Anal. Biochem

J. Biol. Chem

Methods Enzymol

Site specific enzymatic cleavage of RNA

Nucl. Acids Res

Translational potentiation of messenger RNA with secondary structure in Xenopus

Science

Synthetic oligonucleotide tails inhibit in vitro and in vivo translation of SP6 transcripts of maize zein cDNA clones

Nucl. Acids Res

The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency

Genes Develop

A role for mRNA secondary structure in the control of translation initiation

Nature (London)

Analysis of mRNA populations by cDNA. mRNA hybrid-mediated inhibition of cell-free protein synthesis

Unwinding protein specific for mRNA translation fractionated together with rabbit reticulocyte initiation factor 3 complex

Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo

Nature (London)

Article
Translation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon