Transfer RNAs (tRNAs) are a major class of noncoding RNA. Stress-induced cleavage of tRNA is highly conserved and results in tRNA fragments. Here, we found that specific tRNA fragments in plasma are associated with epilepsy. Small RNA-Seq of plasma samples collected during video EEG monitoring of patients with focal epilepsy identified significant differences in 3 tRNA fragments (5′GlyGCC, 5′AlaTGC, and 5′GluCTC) compared with samples from healthy controls. The levels of these tRNA fragments were higher in pre-seizure than in post-seizure samples, suggesting that they may serve as biomarkers of seizure risk in patients with epilepsy. In vitro studies confirmed that production and extracellular release of tRNA fragments were lower after epileptiform-like activity in hippocampal neurons. We designed PCR-based assays to quantify tRNA fragments in a cohort of pre- and post-seizure plasma samples from patients with focal epilepsy and from healthy controls. Receiver operating characteristic analysis indicated that tRNA fragments potently distinguished pre- from post-seizure patients. Elevated levels of tRNA fragments were not detected in patients with psychogenic nonepileptic seizures and did not result from medication tapering. This study potentially identifies a new class of epilepsy biomarker and reveals the possible existence of prodromal molecular patterns in blood that could be used to predict seizure risk.
Marion C. Hogg, Rana Raoof, Hany El Naggar, Naser Monsefi, Norman Delanty, Donncha F. O’Brien, Sebastian Bauer, Felix Rosenow, David C. Henshall, Jochen H.M. Prehn
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at email@example.com.