MoDorado: enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers.

Rapid and accurate identification of transfer RNA (tRNA) modifications is crucial for understanding their role in protein translation and disease. However, their detection on tRNAs is challenging due to high modification density. With the release of the nanopore direct RNA sequencing kit SQK-RNA004, de novo modification calling models became available for pseudouridine (Ψ), m6A, inosine, and m5C, as part of the Dorado basecaller.

The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine.

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.

Queuosine salvage in fission yeast by Qng1-mediated hydrolysis to queuine.

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside that is found at position 34, also known as the wobble position, of tRNAs with a GUN anticodon, and Q ensures faithful translation of the respective C- and U-ending codons. While Q is present in tRNAs in most eukaryotes, only bacteria can synthesize it denovo. In contrast, eukaryotes rely on external sources like their food and the gut microbiome in order to Q-modify their tRNAs, and Q therefore can be regarded as a micronutrient.