An overview of RNAs with regulatory functions in gram-positive bacteria

Abstract

During the last decade, RNA molecules with regulatory functions on gene expression have benefited from a renewed interest. In bacteria, recent high throughput computational and experimental approaches have led to the discovery that 10-20% of all genes code for RNAs with critical regulatory roles in metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many of these RNAs act through binding to their target mRNAs while others modulate protein activity or target DNA. The cis-acting RNAs include regulatory regions of mRNAs that can respond to various signals. These RNAs often provide the missing link between sensing changing conditions in the environment and fine-tuning the subsequent biological responses. Information on their various functions and modes of action has been well documented for gram-negative bacteria. Here, we summarize the current knowledge of regulatory RNAs in gram-positive bacteria.

Fig. 1

Mechanisms of action of trans-acting antisense sRNAs in gram-positive bacteria. a Schematic drawing of antisense RNA-mediated transcription attenuation in plasmid pT181 (according to [155]). The antisense RNA (red) initiates binding with the mRNA (black) by a loop–loop interaction, which rapidly propagates to form a long duplex. The formation of the duplex stabilizes the formation of a transcription terminator and arrests the elongation of transcription. In the absence of the antisense RNA, the mRNA structure forms an anti-terminator structure allowing the synthesis of RepA protein. b Schematic drawing of the antisense RNA Rat-mediated degradation of txpA mRNA from B. subtilis (according to [43]). The antisense RNA is fully complementary to the 3′ end of the mRNA and induces degradation of the target mRNA. c Structure and mechanism of action of the quorum-sensing RNAIII from S. aureus. The secondary structure of RNAIII is from [52] with the three hairpins 7, 13 and 14. RNAIII uses different hairpin motifs to bind various mRNAs encoding virulence factors (protein A, fibrinogen-binding protein SA1000) and the transcriptional regulatory protein Rot. Formation of RNAIII–mRNA complexes blocks the access of the 30S ribosomal subunit and concomitantly recruits the endoribonuclease III to cleave the repressed mRNAs [27]. SD is for Shine–Dalgarno sequence

Fig. 2

Mechanisms of action of cis-acting regulatory regions of mRNAs in gram-positive bacteria. a Transcriptional attenuation (top) and translational (below) control mediated by the binding of a ligand. In the absence of ligand, the mRNA forms an anti-terminator hairpin and transcription proceeds through the open reading frame (ORF), or alternatively, the ribosome binding site (RBS) is available for translation initiation. In the presence of ligand, the sensor domain is stabilized by the direct recognition of ligand, causing the formation of a transcription terminator or alternatively a structure that sequesters the RBS. SD is for Shine–Dalgarno sequence. b L. monocytogenes prfA mRNA is regulated by a temperature-dependent mechanism [115]. At low temperature, the mRNA adopts a secondary structure, which blocks access of the 30S ribosomal subunit. At 37°C, the structure melts, allowing access of the 30S subunit and translation of PrfA, a major transcriptional regulator of virulence gene expression. c The T-box family of tRNA-mediated riboswitches. The uncharged tRNA acts as the signal molecule directly sensed by the 5′ untranslated region of the mRNA. When no uncharged tRNA is sensed, a transcription terminator in the T-box of the controlled mRNA is formed, leading to its transcription termination. Upon sensing of the uncharged tRNA, two interactions (blue) with the leader region including the T-box (red) take place. The first one is the pairing of the uncharged tRNA anticodon with the so-called specifier sequence (S) acting as a codon mimic. The second interaction involves pairing of the 3′CCA end of the tRNA with a complementary sequence in the leader region. As a result, an anti-terminator sequence is stabilized, and continued transcription of the downstream controlled ORF is allowed. T is for terminator and AT for anti-terminator of transcription