Subsystem: Trans-translation by stalled ribosomes

This subsystem's description is:

Subsystem under construction
Note that the "absence" of tmRNA in a number of genomes is not meaningful and is due for the large part to the fact that this RNA feature has not been called in a genome. Such omissions can't be corrected at the moment, since manual RNA editing is not supported currently in SEED.

Quoting (Keiler, 2007):
In bacteria, translating ribosomes frequently reach the end of an mRNA without terminating at a stop codon. In fact, translation of mRNAs that are truncated because of premature termination of transcription, partial degradation, or physical or chemical damage is an unavoidable consequence of co-transcriptional translation. These “nonstop” mRNAs lack translation termination signals, and there is no obvious way to release ribosomes when they reach the 30 end; ribosomes that have stalled at the end of an mRNA are stable in vitro. In vivo, stalled complexes are released so efficiently that the underlying mechanisms are just coming to light, although there are over 13 000 stalling events per cell in each generation (Moore and Sauer, 2005). Clearly, the cell needs to maintain a pool of active ribosomes for new translation, and the ribosomes would be rapidly titrated out of this pool if they could not be released from nonstop mRNAs. In addition, release of incomplete proteins can be toxic to the cell, clogging the chaperone and proteolysis pathways and generating detrimental activities. To combat these problems, all bacteria contain the transfer-messenger RNA (tmRNA) system for efficiently releasing stalled ribosomes and targeting incomplete proteins and mRNAs for degradation. tmRNA is not only universally conserved (Gueneau de Novoa et al., 2004), but is also one of the most abundant RNAs in the cell, and is important for normal physiology in many species.

The tmRNA tagging system tmRNA uses a unique structure to form a ribonucleoprotein complex and interact with stalled ribosomes. The 5-prime and 3-prime ends of tmRNA fold into a structure resembling alanyl-tRNA, and the 3-prime end is charged with alanine by alanyl-tRNA synthetase. However, tmRNA lacks an anticodon stem-loop and is significantly larger than a tRNA, and the remainder of the molecule contains an open reading frame encoding a short peptide tag. Similar to other small regulatory RNAs, there is little identity in tmRNA sequences from distantly related bacteria. However, the alanyl-tRNA-like structure is conserved and most sequences are predicted to contain three to four pseudo-knots. The encoded peptide tags vary in length from 8–35 residues. Most tag sequences begin with alanine and end with two alanine residues, but other positions are not widely conserved. tmRNA is bound by SmpB, a small protein that is required for tmRNA structure, stability, and interaction with the ribosome. Similar to tmRNA, SmpB is present in all known species of bacteria, and in all reported cases the phenotype of cells lacking SmpB is identical to those lacking tmRNA. Alanyl-tmRNA is also bound by EF–Tu in the same manner as a tRNA [11,12]. Other proteins co-purify with the tmRNA/SmpB/EF–Tu complex, but the functional significance of these interactions is unclear.

The model for tmRNA activity:
The alanyl- tmRNA/SmpB/EF–Tu complex enters the A site of ribosomes stalled at the end of an mRNA, acting like a tRNA. The nascent protein is transferred to alanyl-tmRNA, and the peptidyl-tmRNA-SmpB complex is translocated to the P site, placing the tag reading frame in the mRNA channel of the ribosome and releasing the damaged mRNA. Translation resumes on the tmRNA open reading frame and terminates at a stop codon, releasing the nascent protein with the tmRNA-encoded tag at its C-terminus. The efficient dissociation of ribosomes from tmRNA ensures that they can be rapidly recycled for productive translation. In addition to releasing the ribosome, tmRNA activity targets the nascent protein for degradation. The tmRNA-encoded peptide contains epitopes for proteases found in each compartment of the cell, ensuring that the tagged protein will be rapidly degraded if it is released into tagged protein will be rapidly degraded whether it is released into the cytoplasm, translocated into the membrane or exported to the periplasm…”


References

Keiler KC. Biology of trans-translation.Annu Rev Microbiol. 2008;62:133-51. Review.

Hayes CS, Keiler KC. Beyond ribosome rescue: tmRNA and co-translational processes. FEBS Lett. 2010 Jan 21;584(2):413-9. PMID: 19914241

Karzai AW, Sauer RT. 2001. Protein factors associated with the SsrA. SmpB tagging and ribosome rescue complex. Proc Natl Acad Sci USA, 98:3040-3044.

Moore SD, Sauer RT: Ribosome rescue: tmRNA tagging activity and capacity in Escherichia coli. Mol Microbiol 2005, 58:456-466.

Moore SD, Sauer RT. 2007. The tmRNA system for translational surveillance and ribosome rescue. Annu Rev Biochem, 76: doi: 10.1146/annurev.biochem.75.103004.142733.

Gueneau de Novoa P, Williams KP. 2004. The tmRNA website: reductive evolution of tmRNA in plastids and other endosymbionts. Nucleic Acids Res 2004, 32:D104-D108.

For more information, please check out the description and the additional notes tabs, below

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SmpBtmRNA
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Subsystem under construction
Note that the "absence" of tmRNA in a number of genomes is not meaningful and is due for the large part to the fact that this RNA feature has not been called in a genome. Such omissions can't be corrected at the moment, since manual RNA editing is not supported currently in SEED.

Quoting (Keiler, 2007):
In bacteria, translating ribosomes frequently reach the end of an mRNA without terminating at a stop codon. In fact, translation of mRNAs that are truncated because of premature termination of transcription, partial degradation, or physical or chemical damage is an unavoidable consequence of co-transcriptional translation. These “nonstop” mRNAs lack translation termination signals, and there is no obvious way to release ribosomes when they reach the 30 end; ribosomes that have stalled at the end of an mRNA are stable in vitro. In vivo, stalled complexes are released so efficiently that the underlying mechanisms are just coming to light, although there are over 13 000 stalling events per cell in each generation (Moore and Sauer, 2005). Clearly, the cell needs to maintain a pool of active ribosomes for new translation, and the ribosomes would be rapidly titrated out of this pool if they could not be released from nonstop mRNAs. In addition, release of incomplete proteins can be toxic to the cell, clogging the chaperone and proteolysis pathways and generating detrimental activities. To combat these problems, all bacteria contain the transfer-messenger RNA (tmRNA) system for efficiently releasing stalled ribosomes and targeting incomplete proteins and mRNAs for degradation. tmRNA is not only universally conserved (Gueneau de Novoa et al., 2004), but is also one of the most abundant RNAs in the cell, and is important for normal physiology in many species.

The tmRNA tagging system tmRNA uses a unique structure to form a ribonucleoprotein complex and interact with stalled ribosomes. The 5-prime and 3-prime ends of tmRNA fold into a structure resembling alanyl-tRNA, and the 3-prime end is charged with alanine by alanyl-tRNA synthetase. However, tmRNA lacks an anticodon stem-loop and is significantly larger than a tRNA, and the remainder of the molecule contains an open reading frame encoding a short peptide tag. Similar to other small regulatory RNAs, there is little identity in tmRNA sequences from distantly related bacteria. However, the alanyl-tRNA-like structure is conserved and most sequences are predicted to contain three to four pseudo-knots. The encoded peptide tags vary in length from 8–35 residues. Most tag sequences begin with alanine and end with two alanine residues, but other positions are not widely conserved. tmRNA is bound by SmpB, a small protein that is required for tmRNA structure, stability, and interaction with the ribosome. Similar to tmRNA, SmpB is present in all known species of bacteria, and in all reported cases the phenotype of cells lacking SmpB is identical to those lacking tmRNA. Alanyl-tmRNA is also bound by EF–Tu in the same manner as a tRNA [11,12]. Other proteins co-purify with the tmRNA/SmpB/EF–Tu complex, but the functional significance of these interactions is unclear.

The model for tmRNA activity:
The alanyl- tmRNA/SmpB/EF–Tu complex enters the A site of ribosomes stalled at the end of an mRNA, acting like a tRNA. The nascent protein is transferred to alanyl-tmRNA, and the peptidyl-tmRNA-SmpB complex is translocated to the P site, placing the tag reading frame in the mRNA channel of the ribosome and releasing the damaged mRNA. Translation resumes on the tmRNA open reading frame and terminates at a stop codon, releasing the nascent protein with the tmRNA-encoded tag at its C-terminus. The efficient dissociation of ribosomes from tmRNA ensures that they can be rapidly recycled for productive translation. In addition to releasing the ribosome, tmRNA activity targets the nascent protein for degradation. The tmRNA-encoded peptide contains epitopes for proteases found in each compartment of the cell, ensuring that the tagged protein will be rapidly degraded if it is released into tagged protein will be rapidly degraded whether it is released into the cytoplasm, translocated into the membrane or exported to the periplasm…”


References

Keiler KC. Biology of trans-translation.Annu Rev Microbiol. 2008;62:133-51. Review.

Hayes CS, Keiler KC. Beyond ribosome rescue: tmRNA and co-translational processes. FEBS Lett. 2010 Jan 21;584(2):413-9. PMID: 19914241

Karzai AW, Sauer RT. 2001. Protein factors associated with the SsrA. SmpB tagging and ribosome rescue complex. Proc Natl Acad Sci USA, 98:3040-3044.

Moore SD, Sauer RT: Ribosome rescue: tmRNA tagging activity and capacity in Escherichia coli. Mol Microbiol 2005, 58:456-466.

Moore SD, Sauer RT. 2007. The tmRNA system for translational surveillance and ribosome rescue. Annu Rev Biochem, 76: doi: 10.1146/annurev.biochem.75.103004.142733.

Gueneau de Novoa P, Williams KP. 2004. The tmRNA website: reductive evolution of tmRNA in plastids and other endosymbionts. Nucleic Acids Res 2004, 32:D104-D108.