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Oxidation of 5-methylcytosine (5mC) in DNA by the Ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m5C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m5C oxidation in transfer RNA (tRNAs). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm5C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m5C in tRNAs can be readily observed in vitro. We further observed that hm5C levels in tRNA were significantly decreased in Tet2 KO mouse embryonic stem cells (mESCs) in comparison to wild type mESCs. Reciprocally, induced expression of the catalytic domain of TET2 led to an obvious increase in hm5C and a decrease in m5C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m5C oxidation in tRNA promotes translation in vitro. These results suggest TET2 may influence translation through impacting tRNA methylation and reveal an unexpected role for TET enzymes in regulating multiple nodes of the central dogma.

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Traditional orthopaedic devices do not communicate with physicians or patients post-operatively. After implantation, follow-up of traditional orthopaedic devices is generally limited to episodic monitoring. However, the orthopaedic community may be shifting towards incorporation of smart technology. Smart technology in orthopaedics is a term that encompasses a wide range of potential applications. Smart orthopaedic implants offer the possibility of gathering data and exchanging it with an external reader. They incorporate technology that enables automated sensing, measuring, processing, and reporting of patient or device parameters at or near the implant. While including advanced technology in orthopaedic devices has the potential to benefit patients, physicians, and the scientific community, it may also increase the patient risks associated with the implants. Understanding the benefitrisk profile of new smart orthopaedic devices is critical to ensuring their safety and effectiveness. The 2018 FDA public workshop on orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices was held on April 30, 2018, at the FDA White Oak Campus in Silver Spring, MD with the goal of fostering a collaborative dialogue amongst the orthopaedic community. Workshop attendees discussed four key areas related to smart orthopaedic devices: engineering and technology considerations, clinical and patient perspectives, cybersecurity, and regulatory considerations. The workshop presentations and associated discussions highlighted the need for the orthopaedic community to collectively craft a responsible path for incorporating smart technology in musculoskeletal disease care.