Abstract
Negative feedback regulation, that is the ability of a gene to repress its own synthesis, is the most abundant regulatory motif known to biology. Frequently reported for transcriptional regulators, negative feedback control relies on binding of a transcription factor to its own promoter. Here, we report a novel mechanism for gene autoregulation in bacteria relying on small regulatory RNA (sRNA) and the major endoribonuclease, RNase E. TIER-seq analysis (transiently-inactivating-an-endoribonuclease-followed-by-RNA-seq) revealed ~25,000 RNase E-dependent cleavage sites in Vibrio cholerae, several of which resulted in the accumulation of stable sRNAs. Focusing on two examples, OppZ and CarZ, we discovered that these sRNAs are processed from the 3' untranslated region (3' UTR) of the oppABCDF and carAB operons, respectively, and base-pair with their own transcripts to inhibit translation. For OppZ, this process also triggers Rho-dependent transcription termination. Our data show that sRNAs from 3' UTRs serve as autoregulatory elements allowing negative feedback control at the post-transcriptional level.
Highlights
Biological systems function on a mechanism of inputs and outputs, each triggered by and triggering a specific response
We validated our approach by monitoring the expression of two known substrates of ribonuclease E (RNase E) in V. cholerae: A) 5S rRNA, which is processed by RNase E from the 9S precursor rRNA (Papenfort et al, 2015b), and B) the MicX small regulatory RNA (sRNA), which contains two RNase E cleavage sites (Davis and Waldor, 2007)
Accumulation of the two RNase E-dependent processing intermediates of MicX was reduced in the rneTS strain at the non-permissive temperature
Summary
Biological systems function on a mechanism of inputs and outputs, each triggered by and triggering a specific response. Feedback control (a.k.a. autoregulation) is a regulatory principle wherein the output of a system amplifies (positive feedback) or reduces (negative feedback) its own production. Negative feedback regulation is ubiquitous among biological systems and belongs to the most thoroughly characterized network motifs (Nitzan et al, 2017; Shen-Orr et al, 2002). A transcription factor acts to repress its own transcription by blocking access of RNA polymerase to the promoter region. This canonical mode of negative autoregulation is universally present in living systems and in Escherichia coli more than 40% of the known transcription factors are controlled by this type of regulation (Rosenfeld et al, 2002). Several characteristics have been attributed to negative autoregulatory circuits including an altered response time and improved robustness towards fluctuations in transcript production rates (Alon, 2007)
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