RNA Regulation in Streptococcus pneumoniae

In collaboration with the van Opijnen Lab at BC, we are investigating RNA regulation in Streptococcus pneumoniae. We are specifically interested in assessing how structured RNA regulators contribute to the growth and virulence of S. pneumoniae and understanding the relationship between gene regulation and organismal fitness. A new project we’re beginning will examine the impact of inhibiting translation on the secondary structure of RNA regulators in S. pneumoniae using high-throughput approaches.

Transcriptome of S. pneumoniae TIGR4 including transcription start and stop sites mapped to the genome. From Warrier et al. PLoS Pathogens 2018.

Publications:
Warrier et al. The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence. PLoS Pathogens 14(12):e1007461 (2018).[pubmed] [article]

Co-evolution of ribosomal proteins and their mRNA regulatory elements across bacterial phyla

Ribosomal protein operons in Escherichia coli are regulated by a series of structured RNA motifs that enable negative feedback of specific ribosomal proteins on expression of an entire ribosomal protein operon. While these regulators have been known since the early 1980’s in E. coli, it turns out that in diverse phyla of bacteria, there are alternative structures that perform the same function, but have little or no sequence or structural similarity. Our favorite example of this are the suite of four mRNA regulators that precede the gene encoding ribosomal protein S15 in different bacterial species. Using this system we have asked a series of questions that range from understanding the determinants of RNA-protein binding, and determining how these regulators co-evolve with their binding-parter (ribosomal protein S15), to assessing whether these regulators are likely to have arisen independently or have a common ancestor. Our current work is focused on comparing situation with S15, where there are many natural regulators, with cases where a single mRNA structure regulates gene expression across many bacterial phyla.

Diverse RNA regulators that respond to S15 across bacterial phyla

Publications
Pei S et al. Recognizing RNA structural motifs in HT-SELEX data for ribosomal protein S15. BMC Bioinformatics 18(1):298 (2017). [pubmed] [article]
Slinger BL and Meyer MM: RNA regulators responding to ribosomal protein S15 are frequent in sequence space. Nucleic Acids Res 44:9331-9341 (2016). [pubmed] [article]
Slinger BL et al. Co-evolution of bacterial ribosomal protein S15 with diverse mRNA regulatory structures PLoS Genetics 11:e1005720 (2015). [pubmed] [article]

Riboswitch Evolution

Riboswitches are bacterial cis-regulatory elements that interact specifically with small molecules to change gene expression. They are found across nearly all phyla of bacteria, but in different species of bacteria the same ligand-binding domain (aptamer) may have diverse mechanisms of action, and the same small molecule ligand may interact with distinct RNA structures that show little to no conservation. We are exploring this diversity using both comparative genomic, and experimental tools to understand the relationship between nucleotide changes, biological function, and organismal fitness for structured RNA gene regulators.

Model of glycine aptamer evolution in different regulatory contexts. Adapted from Crum et al. PLoS Comp. Biol. 2019.

Publications:
Crum M et al. Regulatory Context Drives Conservation of Glycine Riboswitch Aptamers. PLoS Comp. Biol 15(12):e1007564 (2019) [pubmed] [article]
Babina AM et al. In vivo Behavior of the Tandem Glycine Riboswitch in Bacillus subtilis. mBio 8(5):e01602-17 (2017). [pubmed][article]

Computational identification of novel structured ncRNA elements

RNA regulators are exceedingly diverse across different bacterial species. One of our ongoing efforts is the de novo discovery of structured RNA regulators using comparative genomic approaches. Our most recent work in this area focused on the oral metatranscriptome.

Publications
Ram-Mohan N and Meyer MM: Comparative Metatranscriptomics of Periodontitis Supports a Common Polymicrobial Shift in Metabolic Function and Identifies Novel Putative Disease-Associated ncRNAs. Front Microbiol. 2020: 11:482 [pubmed] [article]
Slinger BL, Deiorio-Hagger K, Anthony J, Gilligan M*,Meyer MM: Discovery and validation of novel and distinct RNA regulators for ribosomal protein S15 BMC Genomics 15:657 (2014). [pubmed] [article]
Pei S, Anthony J, Meyer MM: The structural ensemble neutrality as a feature for structured RNA classification BMC Genomics.16:77 (2015). [pubmed] [article]