Little-known nutrient can boost your brain and fight cancer

Queuosine may sound like a niche detail in a biochemistry textbook, yet this tiny compound touches nearly every corner of human physiology. Scientists have now identified how our cells grab it, opening new paths for research on memory, learning, and cancer resistance.

The work centers on queuosine, a vitamin‑like micronutrient we must borrow from food or friendly gut bacteria.

A reseearch team led by Valérie de Crécy‑Lagard of the University of Florida traced the entry point of queuosine into the cell, the transporter gene SLC35F2.

What is queuosine?

Queuosine is not built into proteins or DNA. Instead, it slots into transfer RNA (tRNA), the molecular interpreters that read genetic codes.

By modifying the wobble position of tRNAs for histidine, tyrosine, aspartate, and asparagine, queuosine helps ribosomes choose the correct amino acid more quickly and accurately. That fine‑tuning keeps translation errors and oxidative stress in check.

Laboratory studies show that supplementing queuosine reverses translation chaos and steadies protein production in stressed cells. Because humans cannot manufacture queuosine, diet and microbes must deliver a steady supply.

Nutrient and cancer connection

Experiments from the German Cancer Research Center uncovered a curious twist. Removing tRNA queuosine weakened context‑based memory in female mice but left males mostly unscathed.

The result hints that queuosine’s control over translation interacts with hormone‑sensitive neural circuits. Cancer biologists track the nutrient for another reason.

Tumor tissues often show steep drops in queuosine modification, a change that encourages the rapid, glycolysis‑heavy metabolism called the Warburg effect. In cultured cells, adding the precursor queuine slows growth in colon, liver, and breast cancer lines.

How queuosine gets in

“For over 30 years, scientists have suspected that there had to be a transporter for this nutrient, but no one could find it. We’ve been hunting for it for a long time,” said de Crécy-Lagard.

Hints about a queuosine gateway surfaced in the early 1990s when growth‑factor stimulation boosted uptake. Screens of known solute carrier proteins drew blanks, sending researchers back to the drawing board.

The investigators ran cross‑species genomics and CRISPR knockouts in human HeLa cells. Only one gene, SLC35F2, consistently blocked uptake when deleted.

Confirming the nutrient’s pathway

Restoring SLC35F2 rescued transport, confirming it as the primary, high‑affinity channel for queuosine and its nucleobase form, queuine.

Radiolabeled assays measured a Michaelis constant of 174 nanomoles, and competing nucleosides failed to displace queuosine from the transporter.

Fluorescence imaging placed SLC35F2 on the plasma membrane and inside the Golgi, a hint that queuosine may cycle through secretory routes before reaching cytosolic tRNA pools.

The study also revealed a second, low‑affinity pathway that kicks in when dietary levels spike.

“We don’t think we could have cracked it without the full team,” said Vincent Kelly of Trinity College Dublin, joint senior author and professor of biochemistry and immunology, highlighting the collaborative push.

Implications for brain health

Neurons fire thousands of times per second, and any slowdown in protein synthesis can scramble that rhythm.

In mice lacking tRNA queuosine, hippocampal neurons mis‑translate codons, depressing long‑term potentiation, a cellular marker of learning.

Restoring dietary queuine fixed the translation lag and improved maze performance within days. With SLC35F2 in hand, neuroscientists can now ask whether genetic variants of the transporter align with neurodevelopmental disorders.

Public databases list rare point mutations in SLC35F2 in fewer than one percent of the population. Their functional impact remains untested, but the data set gives clinicians a starting point for genotype‑phenotype studies.

Could this nutrient help fight cancer?

SLC35F2 carries an intriguing label as an oncogene. High expression predicts poor prognosis in some leukemias and solid tumors.

Researchers once assumed the protein simply imported chemotherapy drugs. Yet new data suggest that tumors may hijack SLC35F2 to starve cells of queuosine and rewire translation. Therapies could exploit the system in two ways.

Selective inhibitors might deprive cancer cells of the nutrient, pushing their error‑prone translation machinery past a lethal threshold.

Alternatively, stabilized queuosine analogs could flood normal tissues that preserve SLC35F2, tamping down oxidative stress and inflammation. Early animal trials are already underway at several labs.

Dietary sources of queuosine

Queuosine comes mainly from meat, dairy, and fermented foods, while some gut bacteria, especially members of the Bacteroides genus, synthesize it from scratch.

Vegans often show slightly lower circulating levels than omnivores, though the difference disappears when microbial producers are abundant.

Antibiotic courses can wipe out those producers for weeks. Researchers in Ireland are now tracking whether short‑term queuosine drops after antibiotics correlate with slower reaction times or mood changes in healthy volunteers.

Cancer drug rides along

SLC35F2 already had a reputation in oncology circles because it escorts the experimental anticancer drug YM155 into cells.

Knowing that the protein’s day job is moving queuosine gives pharmacologists a fresh angle: they can tweak YM155’s structure to ride the same pathway more efficiently.

Conversely, blocking SLC35F2 might protect healthy neurons during chemotherapy by keeping YM155 out while allowing other nucleosides through alternative transporters.

That strategy would echo the way cardiologists use dexrazoxane to shield the heart from doxorubicin, targeting transporter specificity rather than the drug itself.

Gut microbes and queuosine boost health

The discovery also tightens the link between diet, microbes, and host gene expression. If intestinal bacteria ramp up queuosine output, plasma levels rise, SLC35F2 activity increases, and translation fidelity improves.

Better fidelity reduces misfolded proteins that would otherwise inflame the gut, creating a positive feedback loop.

Disrupt the loop with a high‑fat, low‑fiber diet, and queuosine production plummets. Misfolded proteins accumulate, triggering oxidative stress that further damages the gut barrier. Restoring queuosine, through supplements or fermented foods, could break the cycle.

Future research directions

The team wants to chart how queuosine levels rise and fall across organs and over the human lifespan.

High‑throughput mass spectrometry, paired with SLC35F2 genotyping, should reveal whether deficiencies track with cognitive decline or chemotherapy resistance.

“This discovery opens up a whole new chapter in understanding how the microbiome and our diet can influence the translation of our genes,” said Kelly. Diagnostic kits could follow.

A simple blood test measuring queuosine might guide personalized nutrition plans, especially for patients with gut dysbiosis or limited dietary variety.

The study is published in the journal Proceedings of the National Academy of Sciences.

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