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Mechanism of mRNA destabilization by the glmS ribozyme

Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

An array of highly structured domains that function as metabolite-responsive genetic switches has been found to reside within noncoding regions of certain bacterial mRNAs. In response to intracellular fluctuations of their target metabolite ligands, these RNA elements exert control over transcription termination or translation initiation. However, for a particular RNA class within the 5' untranslated region (UTR) of the glmS gene, binding of glucosamine-6-phosphate stimulates autocatalytic site-specific cleavage near the 5' of the transcript in vitro, resulting in products with 2'–3' cyclic phosphate and 5' hydroxyl termini. The sequence corresponding to this unique natural ribozyme has been subjected to biochemical and structural scrutiny; however, the mechanism by which self-cleavage imparts control over gene expression has yet to be examined. We demonstrate herein that metabolite-induced self-cleavage specifically targets the downstream transcript for intracellular degradation. This degradation pathway relies on action of RNase J1, a widespread ribonuclease that has been proposed to be a functional homolog to the well-studied Escherichia coli RNase E protein. Whereas RNase E only poorly degrades RNA transcripts containing a 5' hydroxyl group, RNase J1 specifically degrades such transcripts in vivo. These findings elucidate key features of the mechanism for genetic control by a natural ribozyme and suggest that there may be fundamental biochemical differences in RNA degradation machinery between E. coli and other bacteria.

[Keywords: Riboswitch; ribozyme; RNase J1; Bacillus subtilis; glucosamine-6-phosphate; RNA sensor; mRNA stability]]

Received August 16, 2007; revised version accepted October 24, 2007.

² Corresponding author.

E-MAIL wade.winkler{at}utsouthwestern.edu; FAX (214) 648-8856.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1605307

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