Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.13.1 (exoribonuclease)
 732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNase R readily degrades highly structured RNA, whereas its paralogue, RNase II, is unable to do so. Furthermore, the nuclease domain of RNase R, devoid of all canonical RNA-binding domains, is sufficient for this activity. RNase R also binds RNA more tightly within its catalytic channel than does RNase II, which is thought to be important for its unique catalytic properties. To investigate this idea further, certain residues within the nuclease domain channel of RNase R were changed to those found in RNase II. Among the many examined, we identified one amino acid residue, R572, that has a significant role in the properties of RNase R. Conversion of this residue to lysine, as found in RNase II, results in weaker substrate binding within the nuclease domain channel, longer limit products, increased activity against a variety of substrates and a faster substrate on-rate. Most importantly, the mutant encounters difficulty in degrading structured RNA, pausing within a double-stranded region. Additional studies show that degradation of structured substrates is dependent upon temperature, suggesting a role for thermal breathing in the mechanism of action of RNase R. On the basis of these data, we propose a model in which tight binding within the nuclease domain allows RNase R to capitalize on the natural thermal breathing of an RNA duplex to degrade structured RNAs.
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PMID:Insights into how RNase R degrades structured RNA: analysis of the nuclease domain. 1936 24

The translation machinery deciphers genetic information encoded within mRNAs to synthesize proteins needed for various cellular functions. Defective mRNAs that lack in-frame stop codons trigger non-productive stalling of ribosomes. We investigated how cells deal with such defective mRNAs, and present evidence to demonstrate that RNase R, a processive 3'-to-5' exoribonuclease, is recruited to stalled ribosomes for the specific task of degrading defective mRNAs. The recruitment process is selective for non-stop mRNAs and is dependent on the activities of SmpB protein and tmRNA. Most intriguingly, our analysis reveals that a unique structural feature of RNase R, the C-terminal lysine-rich (K-rich) domain, is required both for productive ribosome engagement and targeted non-stop mRNA decay activities of the enzyme. These findings provide new insights into how a general RNase is recruited to the translation machinery and highlight a novel role for the ribosome as a platform for initiating non-stop mRNA decay.
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PMID:Non-stop mRNA decay initiates at the ribosome. 2109 2

RNase II and RNase R are the two E. coli exoribonucleases that belong to the RNase II super family of enzymes. They degrade RNA hydrolytically in the 3' to 5' direction in a processive and sequence independent manner. However, while RNase R is capable of degrading structured RNAs, the RNase II activity is impaired by dsRNAs. The final end-product of these two enzymes is also different, being 4 nt for RNase II and 2 nt for RNase R. RNase II and RNase R share structural properties, including 60% of amino acid sequence similarity and have a similar modular domain organization: two N-terminal cold shock domains (CSD1 and CSD2), one central RNB catalytic domain, and one C-terminal S1 domain. We have constructed hybrid proteins by swapping the domains between RNase II and RNase R to determine which are the responsible for the differences observed between RNase R and RNase II. The results obtained show that the S1 and RNB domains from RNase R in an RNase II context allow the degradation of double-stranded substrates and the appearance of the 2 nt long end-product. Moreover, the degradation of structured RNAs becomes tail-independent when the RNB domain from RNase R is no longer associated with the RNA binding domains (CSD and S1) of the genuine protein. Finally, we show that the RNase R C-terminal Lysine-rich region is involved in the degradation of double-stranded substrates in an RNase II context, probably by unwinding the substrate before it enters into the catalytic cavity.
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PMID:Swapping the domains of exoribonucleases RNase II and RNase R: conferring upon RNase II the ability to degrade ds RNA. 2146 61

RNase R, an important exoribonuclease involved in degradation of structured RNA, is subject to a novel mechanism of regulation. The enzyme is extremely unstable in rapidly growing cells but becomes stabilized under conditions of stress, such as stationary phase or cold shock. RNase R instability results from acetylation which promotes binding of tmRNA-SmpB, two trans-translation factors, to its C-terminal region. Here, we examine how binding of tmRNA-SmpB leads to proteolysis of RNase R. We show that RNase R degradation is due to two proteases, HslUV and Lon. In their absence, RNase R is stable. We also show, using an in vitro system that accurately replicates the in vivo process, that tmRNA-SmpB is not essential, but it stimulates binding of the protease to the N-terminal region of RNase R and that it does so by a direct interaction between the protease and SmpB which stabilizes protease binding. Thus, a sequence of events, initiated by acetylation of a single Lys residue, results in proteolysis of RNase R in exponential phase cells. RNase R in stationary phase or in cold-shocked cells is not acetylated, and thereby remains stable. Such a regulatory mechanism, dependent on protein acetylation, has not been observed previously in bacterial cells.
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PMID:Transfer-messenger RNA-SmpB protein regulates ribonuclease R turnover by promoting binding of HslUV and Lon proteases. 2287 90