An international team led by scientists from the University of Florida and Trinity College Dublin has identified a long-sought gene that enables human cells to absorb queuosine, a micronutrient essential for brain function, stress response, and potentially cancer prevention.
The discovery, published in PNAS, resolves a 30-year-old mystery and opens the door to targeted therapies that could boost the bioavailability of this rare nutrient. “We’ve been hunting for it for a long time,” said Valérie de Crécy-Lagard, PhD, senior author and professor of microbiology at the University of Florida. “This discovery opens up a whole new chapter in understanding how the microbiome and our diet can influence the translation of our genes.”
A nutrient hidden in plain sight
Queuosine (and its nucleobase form, queuine) is produced exclusively by gut bacteria and must be salvaged from diet or microbiota, as the human body cannot synthesize it. It plays a unique role in modifying transfer RNAs (tRNAs)—molecules responsible for translating genetic information into proteins.
These modifications occur at the “wobble” position of tRNAs, affecting codon–anticodon pairing and, in turn, the accuracy and efficiency of protein synthesis. Recent research has linked queuosine modification to improved neurological function, stress responses, gut health, and reduced cancer risk.
Despite its importance, the exact mechanism by which queuosine enters human cells was unknown—until now.
SLC35F2: the missing piece
Using cross-species genomic analyses and experimental validation in human cells, yeast, and trypanosomes, the researchers identified SLC35F2 as the high-specificity transporter for queuosine and queuine. This solute carrier family gene, previously studied in cancer drug uptake, is now revealed to play a critical physiological role.
In HeLa cells, SLC35F2 was shown to be the sole transporter for queuosine, with high affinity, and a high-specificity importer for queuine. Its localization in both the cell membrane and Golgi apparatus suggests a key role in nutrient trafficking across compartments. Importantly, it does not transport other nucleosides, reinforcing its specificity.
“It´s like a nutrient that fine-tunes how your body reads your genes,” said de Crécy-Lagard. “The idea that this small compound, which people have barely heard of, plays such an important role, is fascinating.”
Toward therapeutic applications
While queuosine is not yet part of routine nutritional assessments, this study highlights its therapeutic potential. Because the transporter SLC35F2 is also implicated in drug uptake and oncogenesis, manipulating its activity could support treatments for cancer, neurodegenerative diseases, or even cognitive enhancement.
The study also underscores the intimate links between gut microbiota, diet, and systemic health. “We have known for a long time that queuosine influences critical processes like brain health, metabolic regulation, cancer and even responses to stress,” said co-senior author Vincent Kelly, PhD, professor in Trinity College Dublin’s School of Biochemistry and Immunology. “But until now we haven’t known how it is salvaged from the gut and distributed to the billions of human cells that take it in.”
Future work may explore dietary supplementation strategies, microbiome engineering, or precision medicine approaches targeting SLC35F2 to harness queuosine’s full potential. For now, researchers hail this discovery as a milestone in molecular nutrition.
