Ménage à trois: post-transcriptional control of the key enzyme for cell envelope synthesis by a base-pairing small RNA, an RNase adaptor protein, and a small RNA mimic.

In Escherichia coli, small RNAs GlmY and GlmZ feedback control synthesis of glucosamine-6-phosphate (GlcN6P) synthase GlmS, a key enzyme required for synthesis of the cell envelope. Both small RNAs are highly similar, but only GlmZ is able to activate the glmS mRNA by base-pairing. Abundance of GlmZ is controlled at the level of decay by RNase adaptor protein RapZ. RapZ binds and targets GlmZ to degradation by RNase E via protein–protein interaction. GlmY activates glmS indirectly by protecting GlmZ from degradation. Upon GlcN6P depletion, GlmY accumulates and sequesters RapZ in an RNA mimicry mechanism, thus acting as an anti-adaptor. As a result, this regulatory circuit adjusts synthesis of GlmS to the level of its enzymatic product, thereby mediating GlcN6P homeostasis. The interplay of RNase adaptor proteins and anti-adaptors provides an elegant means how globally acting RNases can be re-programmed to cleave a specific transcript in response to a cognate stimulus.