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

Sumit Mukherjee,Supratim Sengupta,Danny Barash,Matan Drory Retwitzer

doi:10.1038/s41598-018-23900-7

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.

Highlights

Riboswitches are conserved non-coding structural RNA sensors that bind specific metabolites and regulate gene expression[1,2,3,4]
Our computational approach to detection of TPP riboswitches in fungi and oomycetes is based on the profile Hidden Markov Model26,27. pHMM’s are used to find related sequences containing specific sequence motifs by aligning with a profile generated from a multiple sequence alignment using probabilistic methods
We have found that this type of regulation controls synthesis of NMT1, THI4 and transporter genes in many fungi (Supplementary Data S1) and oomycetes (Supplementary Data S2), where the riboswitch is located in the intronic regions of 5′UTR

Summary

Introduction

Riboswitches are conserved non-coding structural RNA sensors that bind specific metabolites and regulate gene expression[1,2,3,4]. TPP riboswitches were experimentally validated in few species of fungi where they are involved in splicing and regulate the expression of TPP biosynthesis[7,16] and transporter[17] genes. We predict a new type of fungal TPP riboswitches that are located in the 5′UTR of single exonic genes whose mode of regulations does not involve alternative splicing. It is not surprising that TPP riboswitches share similar primary sequence motifs across bacterial and eukaryotic domains This feature was exploited in one of the earliest detection[6] of fungal and plant TPP riboswitches that employed a sequence and structural pattern search using prokaryotic TPP riboswitches as benchmarks and provides additional justification for searching fungal and oomycetes TPP riboswitches using a pHMM constructed from bacterial TPP riboswitches. Our study provides the first comprehensive analysis of the distribution, evolution and regulatory patterns of TPP riboswitches in fungi and oomycetes

Methods

Results

Conclusion