Human health is not only determined by calories, proteins and vitamins, but also by micronutrients that are rare and often underestimated, but that are crucial for driving vital cellular mechanisms. Among the most mysterious are the so called queuine (q) and its subtype containing nucleoside queuosine (Q), which are produced only by bacteria and only taken up by humans through diet and the intestinal microbiome.
For decades, scientists had suspected that there must be a specialized transporter for these micronutrients to get into human cells. Now, a paradigm shifting study published in Proceedings of the National Academy of Sciences (PNAS, 2025) identifies queuine and queuosine as substrates of an oncogene, SLC35F2, the high specificity transporter for these substances.
The finding offers a piece of the puzzle in the biology of nutrients and has far reaching implications for diseases as diverse as neurological disorders and cancer.
What Are Queuosine and Queuine?
Queuine is an altered nucleobase and queuosine is its nucleoside base. Unlike vitamins C or D, queuine cannot be produced by humans. However, it is recovered from the intestinal microbiota or in the food.
Once inside the cell, queuine and queuosine are linked to transfer RNAs (tRNAs) at position 34 of the wobble. This alteration makes it possible to fine tune protein translation for accuracy and efficiency. In addition to this, it also controls processes such as:
Oxidative stress response
Learning and memory
Gut homeostasis
Cell growth and survival
Deficiency of these micronutrients has been associated with neurological dysfunction, and cancer progression.
The Missing Transport Mystery
Previous work demonstrated that queuine could be internalized from the extracellular environment into human cells but the identity of the transporter was unknown. The uptake was found to be highly specific: other purines and nucleosides could not inhibit queuine transport, which suggested the existence of a specific mechanism.
This new study used a combination of comparative genomics, genetic knockouts and cellular imaging to identify the answer: SLC35F2, a solute carrier family protein previously linked to cancer.
Key Findings From the Study
Queuosine is Transported by Only One Transporter, SLC35F2
Knockout experiments in human HeLa cells showed loss of SLC35F2 completely abrogated the uptake of queuosine. This ensured that there is no other path for Q.
High Affinity Queuine Transporter.
SLC35F2 was also found to be the major, high affinity transporter for queuine (Km ~67 nM) whereas a second, lower affinity transporter is present. This dual uptake system may help cells to control uptake under different nutrient conditions.
High Specificity
Competition studies demonstrated that SLC35F2 does not transport the canonical nucleotides adenine, guanine or cytidine. Its action is confined to q and Q, making it very nutritive.
Cellular Localization
Fluorescence labeling revealed that SLC35F2 is localized to the plasma membrane and the Golgi apparatus where it is ideally positioned to regulate nutrient entry and distribution.
Oncogenic Role
Interestingly, SLC35F2 is also an oncogene, and over expressed in several cancers such as lung cancer, thyroid cancer, and bladder cancer. High expression is associated with poor survival
Why Does This Matter?
Basic Science
The finding ends a decades-long puzzle about how queuine and queuosine get into human cells. It also points to the importance of the SLC35 family of transporters, most of which are “orphan” with undefined functions.
Neurological Health
Since queuine is one of the most ubiquitously used cofactors in the brain, perhaps finding out how it is taken up could lead to new treatments for cognitive decline and memory disorders.
Cancer Biology
The association of SLC35F2 with cancer is of particular interest. Expression can lead to increased intracellular levels of q/Q, which can increase tRNA modification and provide tumor cells with a translational benefit. Thus, inhibition of SLC35F2 may be a new anti cancer therapy.
Nutrition & Gut Microbiome
This research puts the gut-cell relationship into focus. Overall, our findings suggest a potential direct relationship between a healthy microbiome and queuine-rich diet and cellular translation machinery and disease risk.
Future Directions
While this discovery is game-changing, there are still many questions left:
Is SLC35F2 activity diet or pharmacologically adjustable?
Does it help people with SLC35F2 defects to take queuine?
Would SLC35F2 inhibitors reduce tumor growth in the cancer types in which it is overexpressed?
What is the function of the secondary low affinity queuine transporter?
Answering these questions will add to the body of knowledge describing the role of microbial metabolites in human health at the molecular level.
Conclusion
For this reason, the identification of SLC35F2 as the queuine and queuosine transporter is a landmark discovery in molecular nutrition and cancer biology. It helps us bridge the gut microbiome, rare micronutrients with oncogenesis.
As scientists continue to determine the role this transporter plays, one thing is certain: even the smallest nutrients can have enormous implications for human health.
References & Resources
Burtnyak, L., Yuan, Y., Stojek, E., et al. (2025). The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine. PNAS, 122(25), e2425364122. https://doi.org/10.1073/pnas.2425364122
Fergus, C., Barnes, D., Alqasem, M. A., & Kelly, V. P. (2015). The queuine micronutrient: Charting a course from microbe to man. Nutrients, 7(4), 2897–2929.
Human Protein Atlas. SLC35F2 expression and cancer prognosis. https://www.proteinatlas.org/ENSG00000110660-SLC35F2/cancer