There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
The endoplasmic reticulum (ER) communicates with the nucleus through the unfolded
protein response (UPR), which senses accumulation of unfolded proteins in the ER lumen
and leads to increased transcription of genes encoding ER-resident chaperones. As
a key regulatory step in this signaling pathway, the mRNA encoding the UPR-specific
transcription factor Hac1p becomes spliced by a unique mechanism that requires tRNA
ligase but not the spliceosome. Splicing is initiated upon activation of Ire1p, a
transmembrane kinase that lies in the ER and/or inner nuclear membrane. We show that
Ire1p is a bifunctional enzyme: in addition to being a kinase, it is a site-specific
endoribonuclease that cleaves HAC1 mRNA specifically at both splice junctions. The
addition of purified tRNA ligase completes splicing; we therefore have reconstituted
HAC1 mRNA splicing in vitro from purified components.