Abstrakt

In silico Identification of Riboswitches in the Human Gut Microbiome for Therapeutic Applications

Priyanka Kumari and Anup Som

Riboswitches are cis-acting, folded non-coding RNA structures which regulate gene expression via conformational changes on binding with specific metabolite. They regulate gene expression of bacteria, archaea, fungi and some plants and may act as potent drug targets. The inhibition of the riboswitches controlling vital genes results in the suppression of growth or death of the organism. Since the normal human gut microbiome comprises of bacterial and archaeal colonies, the inhibition of riboswitches may lead to major changes in the composition of gut microbiome causing diseased condition in human. Therefore, in this study the distribution of various riboswitches, the genes regulated by them and their potential as RNA drug target was explored. The study identified 545 candidate riboswitches in 59 bacterial and 4 archaeal genomes of the adult human gut. The study also revealed that the most abundant riboswitch is the TPP riboswitch (25%) followed by Cobalamin (17%), FMN (11%) and Lysine riboswitch (8%). The lower abundance was shown by YkkC/yxkD leader (2%), Cyclic di-GMP II (1%) and ZMP/ZTP riboswitch (1%); the rare ones included M. Florum (0.4%), Nico (0.2%), AdoCbl variant (0.2%) and SAM-I/IV variant riboswitch (0.2%). Further, the genes regulated by these riboswitches were identified and seven riboswitches such as c-di-GMP I, c-di-GMP II, SAM, glmS, THF, YdaO/ YuaA leader, and glycine riboswitches were predicted as drug targets in the pathogenic bacteria of the human gut.