S-adenosylmethionine-I riboswitch (SAM-I riboswitch) (SAM-I riboswitch)

The S-adenosylmethionine-I (SAM-I) riboswitch is a highly conserved regulatory RNA element found in the 5' untranslated regions of various bacterial mRNAs (Winkler et al., 2003, Nature). It functions as a molecular sensor that directly binds S-adenosylmethionine, the primary methyl donor in cellular metabolism (Montange & Batey, 2006, Nature). Upon binding its ligand, the riboswitch undergoes a structural rearrangement that typically suppresses the expression of genes involved in methionine and SAM biosynthesis. This regulation occurs through mechanisms such as the formation of a transcription terminator hairpin or the sequestration of the ribosome binding site (Blount & Breaker, 2006, Nature Biotechnology). Because these riboswitches are essential for bacterial fitness and are not found in humans, they are considered attractive targets for the development of novel antimicrobial agents. Small molecule analogs of SAM can be designed to bind the riboswitch and constitutively repress vital metabolic pathways, leading to bacterial growth inhibition (Lünse et al., 2014, ChemBioChem). Current research explores these mimetics as potential treatments for infections caused by Gram-positive pathogens. However, challenges remain regarding the specificity of these compounds and the potential for bacteria to develop resistance through mutations in the RNA structure.

Other names

SAM-I leaderS-adenosylmethionine-responsive riboswitchyitJ leaderSAM-binding riboswitch

Ligand binding to the aptamer domain induces a conformational change in the expression platform, leading to transcriptional termination or translational inhibition of downstream metabolic genes (Winkler et al., 2003, Nature).