Divergent stalling sequences sense and control cellular physiology - PubMed (original) (raw)

Review

Divergent stalling sequences sense and control cellular physiology

Koreaki Ito et al. Biochem Biophys Res Commun. 2010.

Abstract

Recent studies have identified several amino acid sequences that interact with the ribosomal interior components and arrest their own elongation. Whereas stalling of the inducible class depends on specific low-molecular weight compounds, that of the intrinsic class is released when the nascent chain is transported across or inserted into the membrane. The stalled ribosome alters messenger RNA secondary structure and thereby contributes to regulation of the cis-located target gene expression at different levels. The stalling sequences are divergent but likely to utilize non-uniform nature of the peptide bond formation reactions and are recruited relatively recently to different biological systems, possibly including those to be identified in forthcoming studies.

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Figures

Fig. 1

Stalling sequences that have been subjected to comprehensive mutational analysis. Sequences that arrest translation elongation are aligned based on their likely positions in the stalled ribosome, with numbering starting inversely from −1 for the position immediately preceding the P-site amino acid. Approximate locations of amino acids in the ribosome are indicated at the top, on the basis of the structure of the extended TnaC peptide–ribosome complex [17]. Note that in the cases of SecM and others, the intraribosomal peptide may be more compacted. Translation ends with the P-site amino acid as the last amino acid of the nascent peptidyl-tRNA (note, however, that ribosomal occupancy has not been determined for MifM). Residues essential for the elongation arrest are underlined. Residues denoted×are less important as they can be changed to one or more different amino acid(s) without affecting the arrest. In all cases that have been examined, the arrest-essential amino acids need to be separated with the exact spacings shown. The A-site amino acids shown in lower case italics are not required for the arrest. The A-site prolines shown in reverse upper case are essential for the arrest. In the case of E. coli TnaC, the A-site codon is a UGA stop (shown by asterisk). 1, Leader peptide of the erythromycin resistance gene, ermC [21]; 2, and 3, arrest sequence of the tryptophanase operon of E. coli [26] and Proteus vulgaris [30], respectively; 4, arrest sequence of SecM from E. coli [38]; 5, a mutant form of the SecM arrest sequence having proline at −4 and −5 positions, of which the one at −4 (italicized) alleviates the specificity of the constriction-proximal residues [39]; 6, arrest sequence of SecM from Mannheimia succiniciproducens [39]; 7, an experimentally evolved arrest sequence obtained by genetic screening [47]; 8, arrest sequence of MifM from B. subtilis [40].

Fig. 2

Arrest regulation. (A) SecM. As translation proceeds, the N-terminal region of the SecM nascent peptide, including the signal sequence (shown by purple thick line), engages in SecA-SecYEG-dependent translocation across the cytoplasmic membrane. When the ribosome attempts to translate the arrest sequence (shown in red thick line), it stalls on the messenger RNA. The stalled ribosome disrupts the secondary structure formed at the secM-secA intergenic region (shown in thin black part in the bottom line, representing the messenger RNA) and consequently exposes the SD sequence (shown in orange) required for translation of secA. Although the elongation arrest is transient in wild-type cells as it is released by active translocation reaction, it is prolonged when the Sec translocation activity is compromised by mutation or at low temperature, exposing the SD sequence for prolonged lengths of time and allowing for enhanced levels of secA translation. It should be noted that the released, completed product of SecM is rapidly proteolyzed in the periplasmic space [57] and that it is not well understood how SecA is able to participate in translocation of ribosome-tethered nascent polypeptide, which might be expected to spatially occlude SecA binding. (B) MifM. Although the situation is similar to the case of SecM shown in (A), there are important differences. MifM contains a predicted Nout–Cin transmembrane sequence (shown by purple thick line), which inserts into the membrane with the aid of the YidC membrane protein integration/folding factor (known as SpoIIIJ in B. subtilis). This mode of MifM membrane insertion is different from the conventional protein export, in which the C-terminus crosses the membrane. The ultimate fate of the released, completed MifM product is unknown.

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Divergent stalling sequences sense and control cellular physiology - PubMed (original) (raw)