RRC ID 4919
Author Deana A, Celesnik H, Belasco JG.
Title The bacterial enzyme RppH triggers messenger RNA degradation by 5' pyrophosphate removal.
Journal Nature
Abstract The long-standing assumption that messenger RNA (mRNA) degradation in Escherichia coli begins with endonucleolytic cleavage has been challenged by the recent discovery that RNA decay can be triggered by a prior non-nucleolytic event that marks transcripts for rapid turnover: the rate-determining conversion of the 5' terminus from a triphosphate to a monophosphate. This modification creates better substrates for the endonuclease RNase E, whose cleavage activity at internal sites is greatly enhanced when the RNA 5' end is monophosphorylated. Moreover, it suggests an explanation for the influence of 5' termini on the endonucleolytic cleavage of primary transcripts, which are triphosphorylated. However, no enzyme capable of removing pyrophosphate from RNA 5' ends has been identified in any bacterial species. Here we show that the E. coli protein RppH (formerly NudH/YgdP) is the RNA pyrophosphohydrolase that initiates mRNA decay by this 5'-end-dependent pathway. In vitro, RppH efficiently removes pyrophosphate from the 5' end of triphosphorylated RNA, irrespective of the identity of the 5'-terminal nucleotide. In vivo, it accelerates the degradation of hundreds of E. coli transcripts by converting their triphosphorylated 5' ends to a more labile monophosphorylated state that can stimulate subsequent ribonuclease cleavage. That the action of the pyrophosphohydrolase is impeded when the 5' end is structurally sequestered by a stem-loop helps to explain the stabilizing influence of 5'-terminal base pairing on mRNA lifetimes. Together, these findings suggest a possible basis for the effect of RppH and its orthologues on the invasiveness of bacterial pathogens. Interestingly, this master regulator of 5'-end-dependent mRNA degradation in E. coli not only catalyses a process functionally reminiscent of eukaryotic mRNA decapping but also bears an evolutionary relationship to the eukaryotic decapping enzyme Dcp2.
Volume 451(7176)
Pages 355-8
Published 2008-1-17
DOI 10.1038/nature06475
PII nature06475
PMID 18202662
MeSH Acid Anhydride Hydrolases / isolation & purification Acid Anhydride Hydrolases / metabolism* Diphosphates / metabolism* Escherichia coli / enzymology* Escherichia coli / genetics* Escherichia coli / metabolism Escherichia coli Proteins / isolation & purification Escherichia coli Proteins / metabolism* Half-Life RNA Stability* RNA, Bacterial / chemistry* RNA, Bacterial / genetics RNA, Bacterial / metabolism* RNA, Messenger / chemistry RNA, Messenger / genetics RNA, Messenger / metabolism
IF 43.07
Times Cited 209
Prokaryotes E. coli ME9062(BW25113) JW2798