Chapter 4 - RNA fragments and brain aging

Abstract

Transfer RNA and ribosomal RNA are known for their traditional roles in translation. Here we reviewed evidence of their novel functionality as sources of short RNA fragments and the emerging role of these fragments as posttranscriptional regulators, including neuronal and aging processes. Such transfer RNA and ribosomal RNA fragments (tRFs and rRFs, respectively) have been shown to change in age-related manner in various model systems (fruit fly, nematode, mouse, rat), similar to the better-studied microRNAs. These fragments are found in Argonaute (Ago) complexes, strongly indicating their role in the RNA-induced silencing complex (RISC) pathway and posttranscriptional gene regulation. Remarkably, their loading in the RISC Ago components changes with age, suggesting age-related alterations in these processes. The biogenesis and mechanism of action of these fragments is still being elucidated, and some early promising results have been obtained in human cells. It appears that a number of their target genes encode proteins relevant in neuronal development and aging and such targets can be predicted using computational approaches. Given the recent advances of potential therapies in various indication areas based on small RNA molecules, we expect this line of research to generate potential novel drugs for aging/neurological applications.