Computational Analysis of Riboswitches: Detection, Distribution and Patterns of Gene Regulation

Mukherjee, Sumit (2019) Computational Analysis of Riboswitches: Detection, Distribution and Patterns of Gene Regulation. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Sumit Mukherjee (15RS047)) 15RS047.pdf - Submitted Version Restricted to Repository staff only Download (7MB)

Abstract

Riboswitches are the cis-regulatory non-coding structural RNA sensors that are present in the 5’ UTRs of the bacterial mRNA. They bind to specific ligands and control the expression of downstream genes/operons. Based on the type of ligand they bind, the mode of regulation of riboswitches reveals a sophisticated mechanism by which bacteria respond to changes in their cellular environment. By considering the high level of sequence conservation of the aptamer domain in each class of riboswitches, we used a pHMM-based method to develop a web-server named Riboswitch Scanner for fast and accurate detection of riboswitches from genomic and metagenomic sequences. The latest version of the Riboswitch Scanner (http://service.iiserkol.ac.in/~riboscan/) can detect 34 different classes of riboswitches and riboswitch regulated genes from the genomic sequences. Next, using the Riboswitch Scanner, we searched all the complete bacterial genomes available in the RefSeq database and performed detailed comparative genomics and phylogenomic analysis for lysine riboswitches. In the process, we were able to correlate the presence of lysine riboswitches with the type of genes that they regulate, which facilitated the reconstruction of the metabolic network of many microbes. Such analysis facilitated the annotation of previously unknown lysine transporter genes. In several instances, we found the evidence of horizontal transfer of lysine riboswitches across distant prokaryotic phyla. Among the near about 40 different classes of riboswitches experimentally detected in bacteria so far, only the TPP riboswitch has been experimentally identified in a few eukaryotes. Further, to understand the distribution and regulatory mechanisms of riboswitches in eukaryotes, we analysed all the available complete fungal and oomycetes genomes from different resources and identified TPP riboswitch-based regulation systems in 138 fungi and 15 oomycetes. Depending on the location of the TPP riboswitches, we classified TPP riboswitch-based gene regulation mechanisms in fungi into four types, of which the first three modes of regulations are based on alternative splicing. Our comprehensive analysis of the distribution, evolution, and regulatory patterns of TPP riboswitches in fungi and oomycetes provides new insights into the riboswitch-based gene regulation in eukaryotes. Next, we developed a database for prokaryotic riboswitches named RiboD (http://ribod.iiserkol.ac.in/) that collates the genome-wide information on 31 different metabolite and ion-sensing riboswitch classes and associated genes/operons from 1777 genomes. The database provides various analysis and searches options to facilitate easy extraction of information associated with riboswitches. RiboD is the first comprehensive database of prokaryotic riboswitches that provides a very useful resource for researchers globally and can be utilized for a better understanding of the riboswitch-based gene regulations in bacteria and archaea.

Actions (login required)

View Item