Amazing stuff! A 30 year old mystery resolved about an important micronutrient. And it's an oncogene.
"... First discovered in the 1970s, queuosine – pronounced “cue-o-scene” – is a vitamin-like micronutrient that human bodies are incapable of making ourselves. Instead, the micronutrient enters the body from food and our gut bacteria. ...
In their research, the team were able to identify SLC35F as the specific gene responsible for transporting the micronutrient around the body that helps translate genetic codes into proteins. ...
The gene has been maintained across millions of years of evolution, being present in both simple, single-cell organisms to modern day humans, indicating its functional importance for life. ..."
"An international team of scientists ... has cracked a decades-old mystery in human biology: how our bodies absorb a micronutrient that we rely on for everything from healthy brain function to cancer defense.
Queuosine – pronounced “cue-o-scene” – is a vitamin-like micronutrient that we can't make ourselves but can only get from food and our gut bacteria. It’s vital to our health, yet its importance went unnoticed for decades. ..."
From the significance and abstract:
"Significance
The identification of SLC35F2 as the eukaryotic transporter of queuine and queuosine is key to understanding how these micronutrients are salvaged from the human gut and distributed to different body tissues. Queuosine modification of transfer RNAs (tRNAs) enhances the accuracy and efficiency of codon–anticodon pairing and regulates a range of biological and pathophysiological states, including oxidative stress responses, cancer, learning, memory, and gut homeostasis.
Abstract
The nucleobase queuine (q) and its nucleoside queuosine (Q) are micronutrients derived from bacteria that are acquired from the gut microbiome and/or diet in humans. Following cellular uptake, Q is incorporated at the wobble base (position 34) of tRNAs that decode histidine, tyrosine, aspartate, and asparagine codons, which is important for efficient translation.
Early studies suggested that cytosolic uptake of queuine is mediated by a selective transporter that is regulated by mitogenic signals, but the identity of this transporter has remained elusive.
Here, through a cross-species bioinformatic search and genetic validation, we have identified the solute carrier family member SLC35F2 as a unique transporter for both queuine and queuosine in Schizosaccharomyces pombe and Trypanosoma brucei.
Furthermore, gene disruption in human HeLa cells revealed that SLC35F2 is the sole transporter for queuosine (Km 174 nM) and a high-affinity transporter for the queuine nucleobase (Km 67 nM), with the additional presence of second low-affinity queuine transporter (Km 259 nM).
Ectopic expression of labeled SLC35F2 reveals localization to the cell membrane and Golgi apparatus via immunofluorescence. Competition uptake studies show that SLC35F2 is not a general transporter for other canonical ribonucleobases or ribonucleosides but selectively imports q and Q.
The identification of SLC35F2, an oncogene, as the transporter of both q and Q advances our understanding of how intracellular levels of queuine and queuosine are regulated and how their deficiency contributes to a variety of pathophysiological conditions, including neurological disorders and cancer."
UF, Trinity College team cracks micronutrient mystery that could be key to brain health, cancer defense (original news release)
The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine (no public access)
Fig. 1 Transport of q and Q into eukaryotes and subsequent intracellular utilization.
Fig. 2 The SLC35F transporter family is functionally diverse.
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