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Two seemingly homologous noncoding RNAs act hierarchically to activate glmS mRNA translation.

Urban JH, Vogel J - PLoS Biol. (2008)

Bottom Line: We show that in wild-type cells, GlmY RNA is unstable due to 3' end polyadenylation; whereas in an E. coli pcnB mutant defective in RNA polyadenylation, GlmY is stabilized and accumulates, which in turn stabilizes GlmZ and causes GlmS overproduction.Our study reveals hierarchical action of two well-conserved sRNAs in a complex regulatory cascade that controls the glmS mRNA.Similar cascades of noncoding RNA regulators may operate in other organisms.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Infection Biology, RNA Biology Group, Berlin, Germany.

ABSTRACT
Small noncoding RNAs (sRNA) can function as posttranscriptional activators of gene expression to regulate stress responses and metabolism. We here describe the mechanisms by which two sRNAs, GlmY and GlmZ, activate the Escherichia coli glmS mRNA, coding for an essential enzyme in amino-sugar metabolism. The two sRNAs, although being highly similar in sequence and structure, act in a hierarchical manner. GlmZ, together with the RNA chaperone, Hfq, directly activates glmS mRNA translation by an anti-antisense mechanism. In contrast, GlmY acts upstream of GlmZ and positively regulates glmS by antagonizing GlmZ RNA inactivation. We also report the first example, to our knowledge, of mRNA expression being controlled by the poly(A) status of a chromosomally encoded sRNA. We show that in wild-type cells, GlmY RNA is unstable due to 3' end polyadenylation; whereas in an E. coli pcnB mutant defective in RNA polyadenylation, GlmY is stabilized and accumulates, which in turn stabilizes GlmZ and causes GlmS overproduction. Our study reveals hierarchical action of two well-conserved sRNAs in a complex regulatory cascade that controls the glmS mRNA. Similar cascades of noncoding RNA regulators may operate in other organisms.

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Related in: MedlinePlus

Pathways of glmS Activation by GlmY and GlmZ RNAs in E. coliModel summarizing the findings of this and previous studies [3–5]. See Discussion for details.
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pbio-0060064-g008: Pathways of glmS Activation by GlmY and GlmZ RNAs in E. coliModel summarizing the findings of this and previous studies [3–5]. See Discussion for details.

Mentions: Figure 8 summarizes the results of this and previous studies [3–5] to suggest a model of how this complex regulatory network may operate in E. coli. NagC-controlled transcription yields a dicistronic glmUS mRNA [15] which undergoes RNase E cleavage in the glmU stop codon sequence to generate monocistronic glmS mRNA [4,5]. This cleavage is independent of the activities of GlmY, GlmZ, Hfq, PAP I, or YhbJ, since the monocistronic glmS mRNA is also detected in strains devoid of any of these factors (Figures 1B and S2). Because the remaining glmU mRNA lacking an intact stop codon is rapidly degraded, most of the cellular GlmU protein seems to be synthesized from the primary glmUS operon mRNA [5]. The glmS mRNA is also quickly turned over unless it becomes stabilized by GlmZ. Whether glmS mRNA is stabilized due to enhanced translation, the GlmZ/glmS RNA interaction, or both, is currently unknown. However, given that the half-life of bacterial mRNA is strongly affected by the association with ribosomes [27,28], increased translation may account for most of the observed glmS mRNA stabilization. The RNA chaperone, Hfq, is essential for glmS translational activation by GlmZ, and is also known to associate in vivo with both GlmZ [8,29] and glmS mRNA (A. Sittka, S. Lucchini, K. Papenfort, C. M. Sharma, J. C. Hinton, and J. Vogel, unpublished data). Regarding glmS, the Hfq function seems to be limited to facilitating the GlmZ/glmS interaction since an hfq mutation does not affect basal glmS expression (Figure 1B and [4]) or glmS mRNA stability (unpublished data).


Two seemingly homologous noncoding RNAs act hierarchically to activate glmS mRNA translation.

Urban JH, Vogel J - PLoS Biol. (2008)

Pathways of glmS Activation by GlmY and GlmZ RNAs in E. coliModel summarizing the findings of this and previous studies [3–5]. See Discussion for details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2267818&req=5

pbio-0060064-g008: Pathways of glmS Activation by GlmY and GlmZ RNAs in E. coliModel summarizing the findings of this and previous studies [3–5]. See Discussion for details.
Mentions: Figure 8 summarizes the results of this and previous studies [3–5] to suggest a model of how this complex regulatory network may operate in E. coli. NagC-controlled transcription yields a dicistronic glmUS mRNA [15] which undergoes RNase E cleavage in the glmU stop codon sequence to generate monocistronic glmS mRNA [4,5]. This cleavage is independent of the activities of GlmY, GlmZ, Hfq, PAP I, or YhbJ, since the monocistronic glmS mRNA is also detected in strains devoid of any of these factors (Figures 1B and S2). Because the remaining glmU mRNA lacking an intact stop codon is rapidly degraded, most of the cellular GlmU protein seems to be synthesized from the primary glmUS operon mRNA [5]. The glmS mRNA is also quickly turned over unless it becomes stabilized by GlmZ. Whether glmS mRNA is stabilized due to enhanced translation, the GlmZ/glmS RNA interaction, or both, is currently unknown. However, given that the half-life of bacterial mRNA is strongly affected by the association with ribosomes [27,28], increased translation may account for most of the observed glmS mRNA stabilization. The RNA chaperone, Hfq, is essential for glmS translational activation by GlmZ, and is also known to associate in vivo with both GlmZ [8,29] and glmS mRNA (A. Sittka, S. Lucchini, K. Papenfort, C. M. Sharma, J. C. Hinton, and J. Vogel, unpublished data). Regarding glmS, the Hfq function seems to be limited to facilitating the GlmZ/glmS interaction since an hfq mutation does not affect basal glmS expression (Figure 1B and [4]) or glmS mRNA stability (unpublished data).

Bottom Line: We show that in wild-type cells, GlmY RNA is unstable due to 3' end polyadenylation; whereas in an E. coli pcnB mutant defective in RNA polyadenylation, GlmY is stabilized and accumulates, which in turn stabilizes GlmZ and causes GlmS overproduction.Our study reveals hierarchical action of two well-conserved sRNAs in a complex regulatory cascade that controls the glmS mRNA.Similar cascades of noncoding RNA regulators may operate in other organisms.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Infection Biology, RNA Biology Group, Berlin, Germany.

ABSTRACT
Small noncoding RNAs (sRNA) can function as posttranscriptional activators of gene expression to regulate stress responses and metabolism. We here describe the mechanisms by which two sRNAs, GlmY and GlmZ, activate the Escherichia coli glmS mRNA, coding for an essential enzyme in amino-sugar metabolism. The two sRNAs, although being highly similar in sequence and structure, act in a hierarchical manner. GlmZ, together with the RNA chaperone, Hfq, directly activates glmS mRNA translation by an anti-antisense mechanism. In contrast, GlmY acts upstream of GlmZ and positively regulates glmS by antagonizing GlmZ RNA inactivation. We also report the first example, to our knowledge, of mRNA expression being controlled by the poly(A) status of a chromosomally encoded sRNA. We show that in wild-type cells, GlmY RNA is unstable due to 3' end polyadenylation; whereas in an E. coli pcnB mutant defective in RNA polyadenylation, GlmY is stabilized and accumulates, which in turn stabilizes GlmZ and causes GlmS overproduction. Our study reveals hierarchical action of two well-conserved sRNAs in a complex regulatory cascade that controls the glmS mRNA. Similar cascades of noncoding RNA regulators may operate in other organisms.

Show MeSH
Related in: MedlinePlus