tRNA fragments are involved in post-stroke immune reactions

tRNA fragments are involved in post-stroke immune reactions

Recently, small RNAs have become more and more interesting for researchers, primarily because of their extensive regulatory functions. To examine these functions in stroke, microRNAs and tRNA fragments in blood samples from ischemic stroke patients collected. "tRNA fragments, which until now were only thought to be debris of the amino acid-transporting tRNAs, have recently been shown to possess biological functions; naturally, we were very interested in that," explains the pharmacologist.

This collaborative effort was able to show, for the first time, the involvement of monocytic tRNA fragments in the poststroke immune response. "Simply put, there may be a 'changing of the guards,' in which tRNA fragments replace microRNAs in monocytes," explains the author.

Electrophoresis-based size-selection followed by qRT-PCR validated the top six up-regulated tRFs in a separate cohort of stroke patients, and independent datasets of small and long RNA sequencing pinpointed immune cell subsets pivotal to these responses, implicating CD14+ monocytes in the cholinergic inflammatory reflex.

In-depth small RNA targeting analyses revealed the most-perturbed pathways following stroke and implied a structural dichotomy between microRNA and tRF target sets. Furthermore, lipopolysaccharide stimulation of murine RAW 264.7 cells and human CD14+ monocytes up-regulated the top six stroke-perturbed tRFs, and overexpression of stroke-inducible tRF-22-WE8SPOX52 using a single-stranded RNA mimic induced down-regulation of immune regulator Z-DNA binding protein 1.

"Bioinformatic network analyses show that these two small RNA species have vastly different functional roles in the immune response, and thus may work in synergy in the regulation of homeostasis."

In the long run, the researchers want to find therapeutics to modify these processes. Indeed, if the immune status of each patient after a stroke could be individually determined, many complications could be avoided.