Gene/Protein
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Drug
Enzyme
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Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0162871 (
abdominal aortic aneurysm
)
8,664
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Transfer messenger RNA (tmRNA; also known as 10Sa RNA or SsrA RNA) is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5' end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to
EF-Tu
after aminoacylation and it enters the ribosome with
EF-Tu
and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with
EF-Tu
and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon-anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of
AAA
(+) proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of non-functional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.
...
PMID:tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell. 2477 39
Uridine 34 (U
34
) at the wobble position of the tRNA anticodon is post-transcriptionally modified, usually to mcm
5
s
2
, mcm
5
, or mnm
5
. The lack of the mcm
5
or s
2
modification at U
34
of tRNA
Lys
, tRNA
Glu
, and tRNA
Gln
causes ribosome pausing at the respective codons in yeast. The pauses occur during the elongation step, but the mechanism that triggers ribosome pausing is not known. Here, we show how the s
2
modification in yeast tRNA
Lys
affects mRNA decoding and tRNA-mRNA translocation. Using real-time kinetic analysis we show that mcm
5
-modified tRNA
Lys
lacking the s
2
group has a lower affinity of binding to the cognate codon and is more efficiently rejected than the fully modified tRNA
Lys
. The lack of the s
2
modification also slows down the rearrangements in the ribosome-
EF-Tu
-GDP-Pi-Lys-tRNA
Lys
complex following GTP hydrolysis by
EF-Tu
. Finally, tRNA-mRNA translocation is slower with the s
2
-deficient tRNA
Lys
. These observations explain the observed ribosome pausing at
AAA
codons during translation and demonstrate how the s
2
modification helps to ensure the optimal translation rates that maintain proteome homeostasis of the cell.
...
PMID:Thio-Modification of tRNA at the Wobble Position as Regulator of the Kinetics of Decoding and Translocation on the Ribosome. 2836 83
