The cyclic phosphodiesterase CNP and RNA cyclase RtcA fine-tune noncanonical XBP1 splicing during ER stress.

ABSTRACT: The activity of X box-binding protein 1 (XBP1), a master transcriptional regulator of endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR), is controlled by a two-step noncanonical splicing reaction in the cytoplasm. The first step of nuclease cleavage by inositol-requiring enzyme 1 (IRE1), a protein kinase/endoribonuclease, is conserved in all eukaryotic cells. The second step of RNA ligation differs biochemically among species. In yeast, tRNA ligase 1 (Trl1) and tRNA 2'-phosphotransferase 1 (Tpt1) act through a 5'-PO₄/3'-OH pathway. In metazoans, RNA 2',3'-cyclic phosphate and 5'-OH ligase (RtcB) ligate XBP1 exons via a 3'-PO₄/5'-OH reaction. Although RtcB has been identified as the primary RNA ligase, evidence suggests that yeast-li

SUBMITTER: Unlu I 

PROVIDER: S-EPMC6302167 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature