A unified view of the initiation of protein synthesis

Nakamoto, Takahisa

doi:10.1016/j.bbrc.2006.01.019

Cited by 50 publications

(42 citation statements)

References 18 publications

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“…This sequence base pairs with the anti-SD sequence in the 16S rRNA of the 30S subunit and positions the mRNA start codon at the P-site of the ribosome (Shine and Dalgarno 1974;Gualerzi et al 2000). In addition to the simple presence of the SD sequence, the physical accessibility of the SD sequence and its associated start codon is a major determinant for translational initiation in prokaryotes (Boni 2006;Nakamoto 2006). The underlying secondary structure of the mRNA can function to prevent initiation at incorrect methionine codons and to facilitate the recognition of the 1 correct initiation codon (Boni 2006;Nakamoto 2006).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the simple presence of the SD sequence, the physical accessibility of the SD sequence and its associated start codon is a major determinant for translational initiation in prokaryotes (Boni 2006;Nakamoto 2006). The underlying secondary structure of the mRNA can function to prevent initiation at incorrect methionine codons and to facilitate the recognition of the 1 correct initiation codon (Boni 2006;Nakamoto 2006). Translational initiation in eukaryotes functions by a different mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

Jones

Wilkinson²,

Hung

et al. 2008

RNA

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The mammalian mitochondrial genome encodes 13 proteins, which are synthesized at the direction of nine monocistronic and two dicistronic mRNAs. These mRNAs lack both 59 and 39 untranslated regions. The mechanism by which the specialized mitochondrial translational apparatus locates start codons and initiates translation of these leaderless mRNAs is currently unknown. To better understand this mechanism, the secondary structures near the start codons of all 13 open reading frames have been analyzed using RNA SHAPE chemistry. The extent of structure in these mRNAs as assessed experimentally is distinctly lower than would be predicted by current algorithms based on free energy minimization alone. We find that the 59 ends of all mitochondrial mRNAs are highly unstructured. The first 35 nucleotides for all mitochondrial mRNAs form structures with free energies less favorable than À3 kcal/mol, equal to or less than a single typical base pair. The start codons, which lie at the very 59 ends of these mRNAs, are accessible within single stranded motifs in all cases, making them potentially poised for ribosome binding. These data are consistent with a model in which the specialized mitochondrial ribosome preferentially allows passage of unstructured 59 sequences into the mRNA entrance site to participate in translation initiation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

Jones

Wilkinson²,

Hung

et al. 2008

RNA

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“…Another, particularly important determinant of translation initiation is mRNA structure. Structure can inhibit translation by hampering the access of the 30S ribosomal subunit to its binding site (ribosome binding site [RBS]) within the TIR (9,29). The affinity of the 30S subunit for the RBS is large enough to iron out weak mRNA structures, and indeed one of the roles of the SD-ASD interaction might be to provide energy for this process (8,40), but beyond a stability threshold an inverse correlation exists between structure stability and translation efficiency (9).…”

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confidence: 99%

The Highly Efficient Translation Initiation Region from the Escherichia coli rpsA Gene Lacks a Shine-Dalgarno Element

et al. 2006

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The translational initiation region (TIR) of the Escherichia coli rpsA gene, which encodes ribosomal protein S1, shows a number of unusual features. It extends far upstream (to position ؊91) of the initiator AUG, it lacks a canonical Shine-Dalgarno sequence (SD) element, and it can fold into three successive hairpins (I, II, and III) that are essential for high translational activity. Two conserved GGA trinucleotides, present in the loops of hairpins I and II, have been proposed to form a discontinuous SD. Here, we have tested this hypothesis with the "specialized ribosome" approach. Depending upon the constructs used, translation initiation was decreased three-to sevenfold upon changing the conserved GGA to CCU. However, although chemical probing showed that the mutated trinucleotides were accessible, no restoration was observed when the ribosome anti-SD was symmetrically changed from CCUCC to GGAGG. When the same change was introduced in the SD from a conventional TIR as a control, activity was stimulated. This result suggests that the GGA trinucleotides do not form a discontinuous SD. Others hypotheses that may account for their role are discussed. Curiously, we also find that, when expressed at moderate level (30 to 40% of total ribosomes), specialized ribosomes are only twofold disadvantaged over normal ribosomes for the translation of bulk cellular mRNAs. These findings suggest that, under these conditions, the SD-anti-SD interaction plays a significant but not essential role for the synthesis of bulk cellular proteins.

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“…It postulates that the initiation site or signal is selected by the base pairing of a nucleotide sequence preceding the initiation codon, currently known as the Shine-Dalgarno (SD) sequence, and a complementary nucleotide sequence at the 3' end of the 30S ribosome's 16S rRNA (the anti-SD sequence). The proposal that a unique nucleotide sequence base pairing was the basis for IS selection was so attractive that the SD mechanism quickly became accepted even without rigorous proof, and even in the presence of conflicting evidences [23].…”

Section: Shine-dalgarno Hypothesis For Prokaryotesmentioning

confidence: 99%

Cumulative Specificity: A Universal Mechanism for the Initiation of Protein Synthesis

Nakamoto¹,

Kézdy²

2012

Cell-Free Protein Synthesis

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A unified view of the initiation of protein synthesis

Cited by 50 publications

References 18 publications

Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

The Highly Efficient Translation Initiation Region from the Escherichia coli rpsA Gene Lacks a Shine-Dalgarno Element

Cumulative Specificity: A Universal Mechanism for the Initiation of Protein Synthesis

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