Nascent chain-mediated localization of mRNA on the endoplasmic reticulum as an important step of unfolded protein response

Kota Yanagitani, Kenji Kohno

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

A system for homeostatic control of proteome, namely proteostasis, in a cell is conserved through a wide range of living organisms. The system is composed of a sensor for misfolded proteins that arise from perturbed proteostasis and signaling machinery that induces the expression of genes for molecular chaperones and proteolytic factors to counterbalance the proteostasis perturbation. In eukaryotes, distinct cellular response mechanisms have been elaborated for perturbed proteostasis within each organelle. In these cases, a sensor molecule recognizes misfolded proteins in the organelle and somehow transmits the signal to the nucleus across the organelle membrane. In the case of the endoplasmic reticulum (ER), proteostatic perturbation is sensed by an ER-resident transmembrane endoribonuclease inositol requiring 1 (IRE1) that catalyzes unconventional splicing of a precursor mRNA on the ER membrane. The resulting spliced form of the mRNA encodes a transcription factor that enters the nucleus and evokes a cellular response to counterbalance the perturbed proteostasis by activating transcription of target genes. In this chapter, we discuss the recently characterized mechanism, in which a nascent polypeptide encoded by the splicing-substrate mRNA directs localization of its own mRNA onto the ER membrane as an essential step for the efficient unconventional splicing of the substrate mRNA upon ER stresses. In particular, we focus on the mechanism that targets the unspliced precursor form of X-box binding protein 1 (XBP1u) mRNA to the ER membrane in metazoan cells. Importantly, translational pausing plays pivotal roles that ensure the nascent chain-mediated ER-targeting of XBP1u mRNA. We also discuss the prerequisites and generality of nascent chain-mediated mRNA localization in the cell.

Original languageEnglish
Title of host publicationRegulatory Nascent Polypeptides
PublisherSpringer Japan
Pages291-310
Number of pages20
ISBN (Electronic)9784431550525
ISBN (Print)4431550518, 9784431550518
DOIs
Publication statusPublished - Apr 1 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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