RNA ligation by RtcB regulates tRNA splicing, the UPR, and axon regeneration.

摘要

Here, I describe the first metazoan loss of function model for RtcB. I began by validating and prioritizing genes proposed to function in axon regeneration. This lead to the discovery of two genes that inhibit axon regeneration, T21 G5.1 and RtcB. After initial characterization of both genes, I focused on the gene with the strongest effect, RtcB. This work shows that RtcB is essential for the ligation of multiple endogenous substrates in metazoans. Specifically, RtcB is the sole RNA ligase capable of ligating endogenous tRNA halves in vivo. I also demonstrate that ligation of the xbp-1 mRNA is essential for activation of the unfolded protein response. Furthermore, my work pioneers the field of RNA ligation as a mechanism for control of axon regeneration. These experiments analyze the function of metazoan RNA ligation at the genetic, cellular, and organismal level. Together, my data suggest that neurons use RtcB in a cell and context dependent way to modify RNA and regulate cellular functions.