A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Schroeder, Griffin M.; Cavender, Chapin E.; Blau, Maya E.; Jenkins, Jermaine L.; Mathews, David H.; Wedekind, Joseph E.

doi:10.1038/s41467-021-27790-8

Title: A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Journal Article · 11 January 2022 · Nature Communications

DOI: https://doi.org/10.1038/s41467-021-27790-8 · OSTI ID:1903961

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University of Rochester, NY (United States). School of Medicine; OSTI
University of Rochester, NY (United States). School of Medicine
University of Rochester, NY (United States)

Riboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ₁-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ₁ riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); University of Rochester, NY (United States). School of Medicine

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Elon Huntington Hooker Graduate Fellowship

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1903961

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 13; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Title: A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

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