Phylogenomic and comparative analysis of the distribution and regulatory patterns of TPP riboswitches in fungi

Abstract

Riboswitches are metabolite or ion sensing cis-regulatory elements that regulate the expression of the associated genes involved in biosynthesis or transport of the corresponding metabolite. Among the nearly 40 different classes of riboswitches discovered in bacteria so far, only the TPP riboswitch has also been found in algae, plants, and in fungi where their presence has been experimentally validated in a few instances. We analyzed all the available complete fungal and related genomes and identified TPP riboswitch-based regulation systems in 138 fungi and 15 oomycetes. We find that TPP riboswitches are most abundant in Ascomycota and Basidiomycota where they regulate TPP biosynthesis and/or transporter genes. Many of these transporter genes were found to contain conserved domains consistent with nucleoside, urea and amino acid transporter gene families. The genomic location of TPP riboswitches when correlated with the intron structure of the regulated genes enabled prediction of the precise regulation mechanism employed by each riboswitch. Our comprehensive analysis of TPP riboswitches in fungi provides insights about the phylogenomic distribution, regulatory patterns and functioning mechanisms of TPP riboswitches across diverse fungal species and provides a useful resource that will enhance the understanding of RNA-based gene regulation in eukaryotes.

TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida

“…While characterizing the small RNAs transcribed in the pathogenic yeast Candida parapsilosis and its relatives [ 19 ] we noted that the RNA structure predictor software Infernal [ 20 ] identified a potential TPP riboswitch in an intron of a poorly characterized gene CPAR2_502100 , which we named DUR31 after its ortholog in Candida albicans [ 21 , 22 ] ( Fig 1A ). Prediction of a riboswitch was surprising, because until very recently, most reports suggest that riboswitches are absent from budding yeasts [ 10 , 12 , 23 ]. We therefore tested the effect of thiamin on splicing of DUR31 in C .…”

“…In eukaryotes only one type of riboswitch has been identified, which binds thiamin pyrophosphate (TPP, a derivative of thiamin). TPP riboswitches regulate expression of thiamin synthesis genes in algae and marine phytoplankton [ 7 ], plants [ 8 , 9 ] and filamentous fungi [ 10 , 11 ], and probably in oomycetes [ 12 ]. Eukaryotic riboswitches are often located within introns, and they function by regulating splicing.…”

“…Until recently, TPP riboswitches have generally been assumed to be absent from budding yeasts (Saccharomycotina), although a few have been predicted bioinformatically [ 12 , 16 – 18 ]. We find that TPP riboswitches are common in DUR31 genes in the Saccharomycotina, and that splicing of this gene in Candida parapsilosis is regulated by thiamin.…”

Alternate RNA Structures

“…Unlike bacterial TPP riboswitches that regulate transcription and translation (Miranda-Rios et al 2001;Mironov et al 2002;Winkler et al 2002), eukaryotic TPP riboswitches are often located in the introns of pre-mRNAs and regulate splicing (Kubodera et al 2003;Cheah et al 2007;Mukherjee et al 2018). These are currently the only known class of eukaryotic riboswitches (Serganov and Nudler 2013).…”

Regulation of the thiamine pyrophosphate (TPP)‐sensing riboswitch in NMT1 mRNA from Neurospora crassa

“…Thiamine pyrophosphate (TPP)‐sensing riboswitches are the most widespread riboswitch class known in bacteria. They have also been identified in fungi , archaea, and plants , and are among the earliest discovered riboswitch representatives. They can regulate gene expression involved in the biosynthesis and transport of the coenzyme thiamine and its phosphorylated derivatives , by controlling messenger RNA translation , and splicing or processing .…”