Abstract
We recently implemented a bioinformatics pipeline that can uncover novel, but rare, riboswitch candidates as well as other noncoding RNA structures in bacteria. A prominent candidate revealed by our initial search efforts was called the 'thiS motif' because of its frequent association with a gene coding for the ThiS protein, which delivers sulfur to form the thiazole moiety of the thiamin precursor HET-P. In the current report, we describe biochemical and genetic data demonstrating that thiS motif RNAs function as sensors of the thiamin precursor HMP-PP, which is fused with HET-P ultimately to form the final active coenzyme thiamin pyrophosphate (TPP). HMP-PP riboswitches exhibit a distinctive architecture wherein an unusually small ligand-sensing aptamer is almost entirely embedded within an otherwise classic intrinsic transcription terminator stem. This arrangement yields remarkably compact genetic switches that bacteria use to tune the levels of thiamin precursors during the biosynthesis of this universally distributed coenzyme.
Highlights
40 distinct riboswitch classes that regulate gene expression in various bacterial species have been experimentally validated to date (McCown et al, 2017; Serganov and Nudler, 2013; Sherwood and Henkin, 2016; Breaker, 2011)
The collection of known riboswitch classes largely sense compounds or ions that are of fundamental importance to organisms from all three domains of life, and these ligands exhibit a bias in favor of compounds that are predicted to be of ancient origin (Breaker, 2012; McCown et al, 2017; Nelson and Breaker, 2017)
We developed a computational pipeline that first identifies the regions of bacterial genomes that are most likely to serve as transcription templates for structured noncoding RNAs, and uses comparative sequence and structural analyses to identify novel candidate RNA motifs (Stav et al, 2019)
Summary
40 distinct riboswitch classes that regulate gene expression in various bacterial species have been experimentally validated to date (McCown et al, 2017; Serganov and Nudler, 2013; Sherwood and Henkin, 2016; Breaker, 2011). The collection of known riboswitch classes largely sense compounds or ions that are of fundamental importance to organisms from all three domains of life, and these ligands exhibit a bias in favor of compounds (enzyme cofactors, RNA nucleotides and their precursors or derivatives) that are predicted to be of ancient origin (Breaker, 2012; McCown et al, 2017; Nelson and Breaker, 2017) If these trends hold, it seems likely that numerous additional riboswitch classes that regulate fundamental biological processes remain to be discovered. The vast majority of these undiscovered riboswitch classes are predicted to be exceedingly rare, and this characteristic is likely to cause difficulties for researchers who seek to identify them To address this challenge, we developed a computational pipeline that first identifies the regions of bacterial genomes that are most likely to serve as transcription templates for structured noncoding RNAs (ncRNAs), and uses comparative sequence and structural analyses to identify novel candidate RNA motifs (Stav et al, 2019).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
