Fig. 3.

Overview of pathways linked to RtcB activity. RtcB can be found in the cytoplasm and the nucleus, enabling it to achieve its functions. [Left] In the cytoplasm, induction of the unfolded protein response in the ER leads to activation of IRE1, which cuts XBP1 mRNA at two stem-loop structures, removing a 26-nucleotide intron. The 5′ and 3′ ends of the cut fragments are ligated with RtcB generating a new mRNA termed spliced XBP1 (XBP1s). Then, the XBP1s transcription factor induces expression of genes involved in protein folding, immunity and lipids regulation. [Middle] In the nucleus, intron-containing pre-tRNAs have to undergo non-conventional splicing events, removing the intron and generating two exon halves. Then, RtcB tRNA ligase activity re-ligates the exon halves, generating a mature tRNA for protein translation. [Right] RtcB has XBP1- and tRNA-independent functions, which remain to be fully elucidated as the RtcB targets linked to these functions and their cellular localisation remain to be identified. These functions could require the presence of some members of the tRNA ligase complex, of which RtcB, RTRAF and DDX1 have been detected in the cytoplasm with and without FAM98B (dotted line)