Walter lab: RNA molecule senses a small metal ion to ramp up bacterium’s detox machine
- News
-
- Search News
-
- Dreyfus-Teacher Scholar Award for Szymczak
- Sanford Named to AAAS
- Biemann Medal for Hakansson
- Sanford Honored with Election to National Academy of Sciences
- McNeil Lab: A more accurate sensor for lead paint
- Schindler Named 2016 Packard Fellow
- Sloan Fellowships for Pratt and Schindler
- Walter Lab: Resolving Subcellular miRNA Trafficking and Turnover at Single-Molecule Resolution
- Maldonado Lab: Cheaper, greener way to grow cystalline seminconductor films
- New polymer allows researchers to study how proteins fold, function
- Researchers focus on cell membranes to develop Alzheimer's treatments
- Video: Research on Lipid Bilayer and Relation to Amyloid-β
- Biteen Lab: Accounting for the "scooching effect"
- Pratt Lab: Molecular Iodine Found in Arctic Atmosphere
- Marsh & McNeil Named AAAS Fellows
- Ramamoorthy Lab: Nanodiscs catch mis-folding amyloid proteins
- Ault Named 2018 Sloan Fellow
- Biteen Lab: Starch Utilization System Assembles around Stationary Starch-Binding Proteins
- Biteen Lab: Starch Utilization System Assembles around Stationary Starch-Binding Proteins
- Pratt & Ault Labs: Harmful algal blooms can become airborne
- Meet Professor Bunsen Burns
- Shedding New Light on Photosynthetic Pigments
- Ruotolo Lab: New Method to ID Proteins
- Energy Research And Education Fuel McCrory CAREER Award
- Building Motors to Drive Nanorobots
- Fast, sensitive mass spectrometer will help UM chemists profile proteins and metabolites
- Award Season for Michigan Chemistry
- Chem Alum Receives Honorary Degree, Gives Rackham Commencement Address
- Alum Named Science Teacher of the Year
- MichiganChem boosts facility for atomic resolution
- DOE Early Career Award for Kerri Pratt
- ACS Honors Alum Weihong Tan
- Michigan Adds Chemistry Education Faculty Position
- Mapp Lab: New research clarifies how ‘fuzzy’ proteins can be used to develop novel drugs
- Karle Symposium Showcases Our Innovative Research
- UM scientists improve synthesis of PET imaging molecules
- MichiganChem Goes to the North Pole
- Diversity Service Award for Nicolai Lehnert
- Two elected Fellows of Royal Society of Chemistry
- Graduate Student Coordinator Honored
- 2018 Mentoring Award Recognizes Unique Programs
- Chen Named AAAS Fellow
- Chem 211 makes organic chem lab real for intro students
- Stephenson Lab: Designing a safer drug building block through photocatalysis
- "Compute-To-Learn" Bridges Classroom to Real-World Experiences
- Meet Roy Wentz: Chemistry's Custom Glassblower
- Michigan Students to Organize American Chemical Society Grad Symposium
- Anna Mapp honored for exceptional efforts to recruit and mentor students from non-traditional backgrounds
- Chemistry Alums Boyd and Pérez-Temprano Named to Talented 12
- Sharing Chemistry with the Community
- Awards Luncheon Offers Recognition for Outstanding Students
- Chemistry Faculty and Staff Collect Honors for Their Work
- Chemistry Writing: More Than Just Lab Reports
- Featured on the UM Gateway: Chemistry D-RISE Alum
- Hot climate, cool science :: Novel instrumentation applied to Arctic atmosphere earns Pratt "40 under 40" honors
- Kennedy Awarded Martin Medal for Achievements in Separation Science
- UM Chemists finding new opportunities in quantum science
- Alumna Sumita Mitra Inducted into National Inventors Hall of Fame
- Walter lab: RNA molecule senses a small metal ion to ramp up bacterium’s detox machine
- Create for Chemistry art contest
- Matzger Lab: A fix for insoluble drugs
- Dope Labs podcast explores the science behind pop culture phenomena
- Travel begets new data and new insights for Michigan Chem grad students
- Kopelman Lab: Nanoparticles + photoacoustic imaging-- a route to better cancer treatment decisions?
- Wang Lab: A productive first year
- National ACS Awards for Four Michigan Faculty
- Montgomery Named Thurnau Professor
- Mental Health, Well-Being and Research
- U-M to 3M: Transitioning to Industry after your PhD
- Chemistry Coping with COVID-19
- Chem Alums Create Crowdfunding Platform
- NSF Graduate Research Fellowships Announced
- Chem Master's Application Re-opened
- Chemistry Awards Announced
- New podcast: "My Fave Queer Chemist”
- Meet Josh Buss
- M|CORE: Preview program lowers barriers to graduate school
- Soellner Joins Michigan Chemistry
- Meet Chem Lecturer Nicole Tuttle
- Archived News
- UM Chemistry Featured Elsewhere
- Events
Bacterial cells use riboswitches--intricate RNA structures that sense the environment of a bacterial cell--for survival by keeping needed trace metals below toxic levels. Certain riboswitches can selectively sense trace metals, such as manganese. Up until this point, researchers had only a vague understanding of how manganese triggers the riboswitch to ramp up the cell’s detox machinery to keep manganese at a safe level.
Now, researchers an international collaboration of researchers have published a thorough visualization of the manganese riboswitch mechanism of action in a study in Nature Communications. They showed that the RNA structure changed when it was bound to manganese, compared to a magnesium atom of similar size and charge. This shift in binding results in a change in the number of proteins that are synthesized in the cell.
This work has important implications due to the prevalence of bacteria in everyday life, explained Chemistry professor Nils Walter, a corresponding author on the publication. One way that bacteria survive is by using riboswitches, which require trace metals. “Like any living organism, bacteria need trace metal elements, which are like the ones we take in vitamin tablets. Bacteria often regulate their metal uptake using riboswitches,” Walter said.
Examples of commonly studied biological metals are iron and zinc, but RNA researchers have been especially interested in manganese (Mn). Another element, magnesium (Mg), is a similarly sized metal, and both Mn and Mg in the cell typically have a doubly positive charge (2+). The chemical similarity of these two elements and their effects on RNA structure is central to the recent Nature Communications study. Mg2+ is required for a range of cellular functions, but is less toxic than Mn2+ and accumulates to higher levels in the cell, so how the RNA senses Mn2+ in this excess of Mg2+ is something that researchers have not understood thus far. “How can an RNA find the Mn2+ in a sea of Mg2+? There were hints in a previous crystal structure that there were tiny chemical differences between Mn2+ and Mg2+ that could be exploited,” Dr. Walter explained.
However, visualizing these chemical differences has been a challenge due to the size difference between the small Mn2+ or Mg2+ ions and the large, complex RNA structure. “Mn2+ is extremely small—it’s just one atom,” Walter said. “An RNA, by comparison, has thousands of atoms. So how does this little tiny metal ion connect to the machinery that reads out this RNA and ultimately produces a protein? It is a David versus Goliath story.”This work has important implications due to the prevalence of bacteria in everyday life, explained Chemistry professor Nils Walter, a corresponding author on the publication. One way that bacteria survive is by using riboswitches, which require trace metals. “Like any living organism, bacteria need trace metal elements, which are like the ones we take in vitamin tablets; bacteria often regulate their metal uptake using riboswitches,” Walter said.
Their work required catching RNA riboswitches in different binding states and identifying their structures. “We were able to show that the RNA can sense whether the site is occupied by Mn2+ or the competing Mg2+ ion because the RNA gets ‘locked down’, and the Mn2+ holds the folded RNA together like a linchpin,” Walter explained.Essentially, RNA can fold and unfold to allow ions to try out that specific site. Mg2+ ions will occupy the site at times due to their sheer number in the cell, but RNA will not be in a stable “locked position” until a Mn2+ occupies the site. Further downstream in the protein-making process, the RNA cannot express the protein unless it is in the “locked position”, meaning the RNA must have a Mn2+ ion bound for protein production.
“What our story is about is learning that the tiny Mn2+ is being caught by the large RNA structure in hair-trigger fashion… Which induces the downstream expression of proteins that appear in the cell,” Walter said. “Such an increase in concentration of a key export protein has serious consequences on the survival of the bacterium by detoxifying excess Mn2+.”
“This work could have applications in the medical field,” Dr. Walter explained. “Bacteria live in our soil, in our bodies, and they are a single cell, which means they alone have to gate or guard what’s coming in and what’s going out.” One way to disrupt certain bacteria that cause diseases in humans or animals is changing their manganese levels. “Could we trick them into thinking they don’t have enough Mn2+, so they import more and die? This idea is a potential path to a new antibiotic.”
This research study was a collaboration across universities and nations, born of a collegial relationship between professors over several years and projects. “Science, nowadays, is a very collaborative effort,” Walter pointed out. “On some level, it’s because we are becoming more specialized, which allows us to dig much deeper into the science, which then is countered by joining forces as we were able to achieve here,” he said.
This work is a collaboration of University of Michigan, Cornell University, Czech Academy of Sciences, and Palacky University
Publication: Nature Communications DOI: 10.1038/s41467-019-12230-5
Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch
This work was funded by NIH R01 grants, ERDF from the Grant Agency of the Czech Republic, and Palacky University.