An overview of gene regulation in bacteria by small RNAs derived from mRNA 3′ ends

Abstract

Over the past two decades, small non-coding RNAs (sRNAs) that regulate mRNAs by short base pairing have gone from a curiosity to a major class of post-transcriptional regulators in bacteria. They are integral to many stress responses and regulatory circuits, affecting almost all aspects of bacterial life. Following pioneering sRNA searches in the early 2000s, the field quickly focused on conserved sRNA genes in the intergenic regions of bacterial chromosomes. Yet, it soon emerged that there might be another rich source of bacterial sRNAs: processed 3’ end fragments of mRNAs. Several such 3’ end-derived sRNAs have now been characterized, often revealing unexpected, conserved functions in diverse cellular processes. Here, we review our current knowledge of these 3’ end-derived sRNAs: their biogenesis through ribonucleases, their molecular mechanisms, their interactions with RNA-binding proteins, and their functional scope, which range from acting as specialized regulators of single metabolic genes to constituting entire non-coding arms in global stress responses. Recent global RNA interactome studies suggest that the importance of functional 3’ end-derived sRNAs has been vastly underestimated, and that this type of cross-regulation between genes at the mRNA level is more pervasive in bacteria than currently appreciated.

RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance

“…Examples of trans -acting regulatory sRNAs encoded within 3′UTRs have recently been described 46 , 47 . These 3′UTR sRNAs can be transcribed as independent transcripts or released from the mRNA by RNase cleavage, and function independently of the parent mRNA 48 . Here we find that the vigR 3′UTR is neither independently transcribed, nor processed from the vigR mRNA indicating that it is a regulatory mRNA.…”

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

“…mRNA-derived sRNAs have emerged from diverse regions of mRNAs (Adams & Storz, 2020). In enterobacteria, 3’ sUTR often binds with RNA chaperones Hfq and ProQ, thus serving as a reservoir of functional sRNAs (Miyakoshi et al , 2015b; Ponath et al , 2022). Surprisingly, regardless of Hfq functionality, 3’UTR-derived sRNAs are also found in Gram-positive bacteria (Fuchs et al , 2021; Desgranges et al , 2022; Lalaouna et al , 2019).…”

“…In addition to intergenic regions of bacterial genomes, mRNA 3’ sUTRs have emerged as a reservoir of an emerging class of post-transcriptional regulators (Miyakoshi et al , 2015b; Adams & Storz, 2020; Ponath et al , 2022). Indeed, the gltIJKL operon encoding the Glu/Asp ABC transporter is transcribed from σ 70 - and σ 54 -dependent promoters, and the gltI mRNA with a Rho-independent terminator is processed by RNase E to release SroC sRNA from its 3’UTR (Miyakoshi et al , 2015a).…”

Small non-coding RNA Interactome Capture reveals pervasive, carbon source-dependent tRNA engagement of yeast glycolytic enzymes

“…To the best of our knowledge, snRIC 2C represents the first method for the systematic isolation of RBPs based on the lengths of their target RNAs. snRIC 2C may also be of particular interest for the field of bacterial small RNA metabolism, as small non-coding RNAs are highly recognized for their critical regulatory roles in bacteria (Jørgensen et al2020, Ponath et al2022, Quendera et al2020), but methods to identify and study their associated RBPs are still needed.…”