Determinants of translational fidelity and efficiency in vertebrate mRNAs

Abstract

m This article reviews current knowledge on the mechanisms affecting the fidelity of initiation codon selection, and discusses the effects of structural features in the 5'-non-coding region on the efficiency of translation of messenger RNA molecules.initiation of translation / scanning model / mRNA structure

Implication of BRCA2 -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53codon 72 Arg>Pro polymorphism

“…The analysis of the 5' UTR for the RNA secondary structure by two different programs showed that the presence of G at -26 stabilized the loop at the vicinity of the translation start site, which could decrease the efficiency of the translation and thereby decrease the expression of BRCA2 . This finding of ours is supported by the classic work of Vega Laso and colleagues [ 47 ] and Kozak [ 48 ], who have argued that the extent of a hairpin negative effect on eukaryotic mRNA translation in vivo depends upon its stability and localization within the molecule.…”

Implication of BRCA2 -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53codon 72 Arg>Pro polymorphism

“…The analysis of the 5' UTR for the RNA secondary structure by two different programs showed that the presence of G at -26 stabilized the loop at the vicinity of the translation start site, which could decrease the efficiency of the translation and thereby decrease the expression of BRCA2 . This finding of ours is supported by the classic work of Vega Laso and colleagues [ 47 ] and Kozak [ 48 ], who have argued that the extent of a hairpin negative effect on eukaryotic mRNA translation in vivo depends upon its stability and localization within the molecule.…”

Initiation of translation and cellular localization of Theileria annulata casein kinase IIα: Implication for its role in host cell transformation

“…Thus, in accordance with the first‐ATG rule (Kozak, 1995) it can be concluded that in vivo translation starts from the second potential start site of the Ta CKIIα gene resulting in a product which contains the whole catalytic core region but lacks the predicted N‐terminal tail including the possible signal peptide. In line with the experimental evidence, critical adjacent nucleotides at position −3 G and +4 G relative to the second potential start codon (corresponding to amino acid position 73) indeed reveal that this site is expected to promote initiation (Kozak, 1994). A favorable sequence context (−3 C and +4 G) for translation start may also be found in the third potential start codon (corresponding to amino acid position 76).…”

Identification of an Alternatively Spliced Seprase mRNA That Encodes a Novel Intracellular Isoform

“…This strongly suggests that the expression of the downstream coding sequence (seprase-s) involves 40 S subunit reinitiation, which is consistent with the decreased translational efficiency exhibited by the pA12 transcripts (49,61).…”

Implication of BRCA2 -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53codon 72 Arg>Pro polymorphism

“…The analysis of the 5' UTR for the RNA secondary structure by two different programs showed that the presence of G at -26 stabilized the loop at the vicinity of the translation start site, which could decrease the efficiency of the translation and thereby decrease the expression of BRCA2 . This finding of ours is supported by the classic work of Vega Laso and colleagues [ 47 ] and Kozak [ 48 ], who have argued that the extent of a hairpin negative effect on eukaryotic mRNA translation in vivo depends upon its stability and localization within the molecule.…”

Initiation of translation and cellular localization of Theileria annulata casein kinase IIα: Implication for its role in host cell transformation

“…Thus, in accordance with the first‐ATG rule (Kozak, 1995) it can be concluded that in vivo translation starts from the second potential start site of the Ta CKIIα gene resulting in a product which contains the whole catalytic core region but lacks the predicted N‐terminal tail including the possible signal peptide. In line with the experimental evidence, critical adjacent nucleotides at position −3 G and +4 G relative to the second potential start codon (corresponding to amino acid position 73) indeed reveal that this site is expected to promote initiation (Kozak, 1994). A favorable sequence context (−3 C and +4 G) for translation start may also be found in the third potential start codon (corresponding to amino acid position 76).…”

Identification of an Alternatively Spliced Seprase mRNA That Encodes a Novel Intracellular Isoform

“…This strongly suggests that the expression of the downstream coding sequence (seprase-s) involves 40 S subunit reinitiation, which is consistent with the decreased translational efficiency exhibited by the pA12 transcripts (49,61).…”

Implication of BRCA2 -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53codon 72 Arg>Pro polymorphism

“…The analysis of the 5' UTR for the RNA secondary structure by two different programs showed that the presence of G at -26 stabilized the loop at the vicinity of the translation start site, which could decrease the efficiency of the translation and thereby decrease the expression of BRCA2 . This finding of ours is supported by the classic work of Vega Laso and colleagues [ 47 ] and Kozak [ 48 ], who have argued that the extent of a hairpin negative effect on eukaryotic mRNA translation in vivo depends upon its stability and localization within the molecule.…”

Initiation of translation and cellular localization of Theileria annulata casein kinase IIα: Implication for its role in host cell transformation

“…Thus, in accordance with the first‐ATG rule (Kozak, 1995) it can be concluded that in vivo translation starts from the second potential start site of the Ta CKIIα gene resulting in a product which contains the whole catalytic core region but lacks the predicted N‐terminal tail including the possible signal peptide. In line with the experimental evidence, critical adjacent nucleotides at position −3 G and +4 G relative to the second potential start codon (corresponding to amino acid position 73) indeed reveal that this site is expected to promote initiation (Kozak, 1994). A favorable sequence context (−3 C and +4 G) for translation start may also be found in the third potential start codon (corresponding to amino acid position 76).…”

Identification of an Alternatively Spliced Seprase mRNA That Encodes a Novel Intracellular Isoform

“…This strongly suggests that the expression of the downstream coding sequence (seprase-s) involves 40 S subunit reinitiation, which is consistent with the decreased translational efficiency exhibited by the pA12 transcripts (49,61).…”