Ribosome‐messenger recognition in the absence of the Shine‐Dalgarno interactions

Tzareva, N.V.; Makhno, V.I.; Boni, Irina V.

doi:10.1016/0014-5793(94)80271-8

Cited by 102 publications

(77 citation statements)

References 26 publications

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“…All these mRNAs carried the same coding sequence. One of these control mRNAs had the 5Ј-UTR of beta-actin mRNA, whereas another one carried a totally unstructured (CAA) 19 5Ј leader (27). The cIlacZ mRNA was translated with similar efficiency, whether it was capped or uncapped.…”

Section: Resultsmentioning

confidence: 99%

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A Leaderless mRNA Can Bind to Mammalian 80S Ribosomes and Direct Polypeptide Synthesis in the Absence of Translation Initiation Factors

Andreev

Terenin

Dunaevsky

et al. 2006

Molecular and Cellular Biology

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Translation initiation in eukaryotic cells is known to be a complex multistep process which involves numerous protein factors. Here we demonstrate that leaderless mRNAs with initiator Met-tRNA can bind directly to 80S mammalian ribosomes in the absence of initiation factors and that the complexes thus formed are fully competent for the subsequent steps of polypeptide synthesis. We show that the canonical 48S pathway of eukaryotic translation initiation has no obvious advantage over the 80S pathway of translation initiation on leaderless mRNAs and suggest that, in the presence of competing mRNAs containing a leader, the latter mechanism will be preferred. The direct binding of the leaderless mRNA to the 80S ribosome was precluded when such an mRNA was supplied with a 5 leader, irrespective of whether it was in a totally single-stranded conformation or was prone to base pairing. The striking similarity between the mechanisms of binding of leaderless mRNAs with mammalian 80S or bacterial 70S ribosomes gives support to the idea that the alternative mode of translation initiation used by leaderless mRNAs represents a relic from early steps in the evolution of the translation apparatus.More than a decade ago, we showed using the toeprint assay that the prokaryotic leaderless mRNA coding for the cI repressor of lambda phage assisted by initiator Met-tRNA was able to bind directly to undissociated 70S ribosomes in the absence of initiation factor 1 (IF1), IF2, and IF3 (1). Under the same conditions, no initiation complex was observed with the 30S ribosomal subunit. In the presence of initiation factors, the 30S subunit invariably bound to internal sites on the mRNA immediately downstream of the closest Shine-Dalgarno (SD) sequence, whereas undissociated 70S ribosome strongly preferred the initiation triplet as close as possible to the 5Ј end of the mRNA. These studies were substantially extended and confirmed in other laboratories both in vitro and in vivo (12,13,15,28) and resulted in similar conclusions. Natural leaderless mRNAs have been identified in all kingdoms of life (see references 10 and 11). This class of mRNAs is well represented in archaea and mammalian mitochondria. Although they have not yet been found among cellular mammalian mRNAs, leaderless monocistronic N and dicistronic N-P RNAs of measles virus were found to be associated with polysomes in infected mammalian cells (4). In addition, it is unlikely that a systematic search for such mRNAs in mammalian cells has ever been undertaken. There is one well-documented example of a translatable leaderless mRNA in unicellular eukaryotes. It encodes a variant specific surface protein of Giardia lamblia and is certainly translated in these cells (14). Leaderless mRNAs are efficiently translated in mammalian cell-free systems (see reference 12). However, it is not known whether they use a similar (80S) pathway for translation initiation in eukaryotes, given the remarkable quantitative and qualitative differences in the organization of eukaryotic and prokaryotic t...

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Section: Resultsmentioning

confidence: 99%

“…The construct pCAA-cIlacZ was obtained using plasmid pCAA-GUS (27) by replacement of the GUS-coding sequence with the coding sequence from pcIlacZ. For the construction of pbAct-cIlacZ, the coding sequence of plasmid pAbG (6) was replaced by that from pcIlacZ in the same way as that for the construct pCAAcIlacZ.…”

Section: Methodsmentioning

confidence: 99%

A Leaderless mRNA Can Bind to Mammalian 80S Ribosomes and Direct Polypeptide Synthesis in the Absence of Translation Initiation Factors

Andreev

Terenin

Dunaevsky

et al. 2006

Molecular and Cellular Biology

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“…2A). The single-stranded conformation of the (CAA) n sequence has been established by enzymatic probing (66). Four other mRNAs, (CAA) n -Stem-GUS, contain GC-rich stems with stabilities ranging from Ϫ5.5 to Ϫ27.6 kcal/mol and flanked by CAA repeats (Fig.…”

Section: Cgp Inhibits De Novo Phosphorylation Of Eif4e Inmentioning

confidence: 99%

Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5′-Terminal Cap and Hairpin

Korneeva

Song

Gram

et al. 2016

Journal of Biological Chemistry

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The MAPK-interacting kinases 1 and 2 (MNK1 and MNK2) are activated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) or p38 in response to cellular stress and extracellular stimuli that include growth factors, cytokines, and hormones. Modulation of MNK activity affects translation of mRNAs involved in the cell cycle, cancer progression, and cell survival. However, the mechanism by which MNK selectively affects translation of these mRNAs is not understood. MNK binds eukaryotic translation initiation factor 4G (eIF4G) and phosphorylates the cap-binding protein eIF4E. Using a cell-free translation system from rabbit reticulocytes programmed with mRNAs containing different 5-ends, we show that an MNK inhibitor, CGP57380, affects translation of only those mRNAs that contain both a cap and a hairpin in the 5-UTR. Similarly, a C-terminal fragment of human eIF4G-1, eIF4G(1357-1600), which prevents binding of MNK to intact eIF4G, reduces eIF4E phosphorylation and inhibits translation of only capped and hairpin-containing mRNAs. Analysis of proteins bound to m 7 GTP-Sepharose reveals that both CGP and eIF4G(1357-1600) decrease binding of eIF4E to eIF4G. These data suggest that MNK stimulates translation only of mRNAs containing both a cap and 5-terminal RNA duplex via eIF4E phosphorylation, thereby enhancing the coupled cap-binding and RNA-unwinding activities of eIF4F.The rate of translational initiation in eukaryotic cells depends on both cis-acting features of individual mRNAs, such as the cap, poly(A) tract, and untranslated regions (UTRs), and trans-acting components, such as initiation factors, protein kinases, and microRNAs (1-3). The recruitment of capped mRNAs to 48S initiation complexes involves several discrete steps that include cap recognition by eukaryotic translation initiation factor 4E (eIF4E), 3 mRNA binding by eIF4G, ATP-dependent unwinding of 5Ј-terminal secondary structure by the helicase eIF4A in concert with eIF4B and eIF4H, recognition of the 3Ј-terminal poly(A) tract by poly(A)-binding protein (PABP), and binding of eIF4G to the 40S ribosomal subunit through eIF3. Both the primary and secondary structure of the 5Ј-UTR are capable of modulating translational efficiency (4, 5). mRNAs containing short 5Ј-UTRs with little secondary structure or terminal oligopyrimidine tracts are more efficiently translated under normal conditions with a limited level of eIF4E. Translational efficiency is diminished in mRNAs containing long, GϩC-rich, and highly structured 5Ј-UTRs because of the necessity for energy-dependent unwinding prior to start codon recognition (6). Translation of these mRNAs requires high levels of eIF4F, the complex of eIF4E, eIF4A, and eIF4G (3, 7). The availability of eIF4E to enter the eIF4F complex is regulated by the PI3K/Akt/mTOR signaling cascade; eIF4E is sequestered by binding to the 4E-BPs, but activation of the mTOR kinase causes phosphorylation of the 4E-BPs and release of eIF4E (8, 9). The activity of eIF4E can be also regulated by phosphorylation via the mitogen-activat...

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“…However, E. coli ribosomal protein S1 has been shown to bind to the TMV leader sequence (Tzareva et al, 1994) or suggested to interact with the Mycoplasma tuf enhancer (Ringquist et al, 1995). S1 can bind to U-rich mRNA sequences or recognize specific RNA structures, which may allow ribosome binding in the absence of an SD interaction (Tzareva et al, 1994;Ringquist et al, 1995;Voorma, 1996). In other words, S1 acting as a 'bridge' to facilitate contacts between the mRNA and small ribosomal subunits may account for the observed stimulatory effects of these two upstream enhancer elements.…”

Section: Alternative Mechanisms That May Contribute To Selection Of Imentioning

confidence: 99%

Functional importance of RNA interactions in selection of translation initiation codons

Sprengart

Porter

1997

Molecular Microbiology

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SummaryRNA base pairing between the initiation codon and anticodon loop of initiator tRNA is essential but not sufficient for the selection of the 'correct' mRNA translational start site by ribosomes. In prokaryotes, additional RNA interactions between small ribosomal subunit RNA and mRNA sequences just upstream of the start codon can efficiently direct the ribosome to the initiation site. Although there is presently no proof for a similar important ribosomal RNA interaction in eukaryotes, the 5Ј non-coding regions of their mRNAs and 'consensus sequences' surrounding initiation codons have been shown to be strong determinants for initiation-site selection, but the exact mechanisms are not yet understood. Intramolecular base pairing in mRNA and participation of translation initiation factors can strongly influence the formation of mRNA-small ribosomal subunit-initiator tRNA complexes and modulate translational activities in both prokaryotes and eukaryotes. Only recently has it been appreciated that alternative mechanisms may also contribute to the selection of initiation codons in all organisms. Although direct proof is currently lacking, there is accumulating evidence that additional cis-acting mRNA elements and trans-acting proteins may form specific 'bridging' interactions with ribosomes during translation initiation.

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Ribosome‐messenger recognition in the absence of the Shine‐Dalgarno interactions

Cited by 102 publications

References 26 publications

A Leaderless mRNA Can Bind to Mammalian 80S Ribosomes and Direct Polypeptide Synthesis in the Absence of Translation Initiation Factors

A Leaderless mRNA Can Bind to Mammalian 80S Ribosomes and Direct Polypeptide Synthesis in the Absence of Translation Initiation Factors

Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5′-Terminal Cap and Hairpin

Functional importance of RNA interactions in selection of translation initiation codons

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