RRC ID 46330
著者 Kanda S, Yanagitani K, Yokota Y, Esaki Y, Kohno K.
タイトル Autonomous translational pausing is required for XBP1u mRNA recruitment to the ER via the SRP pathway.
ジャーナル Proc Natl Acad Sci U S A
Abstract Unconventional mRNA splicing on the endoplasmic reticulum (ER) membrane is the sole conserved mechanism in eukaryotes to transmit information regarding misfolded protein accumulation to the nucleus to activate the stress response. In metazoans, the unspliced form of X-box-binding protein 1 (XBP1u) mRNA is recruited to membranes as a ribosome nascent chain (RNC) complex for efficient splicing. We previously reported that both hydrophobic (HR2) and translational pausing regions of XBP1u are important for the recruitment of its own mRNA to membranes. However, its precise location and the molecular mechanism of translocation are unclear. We show that XBP1u-RNC is specifically recruited to the ER membrane in an HR2- and translational pausing-dependent manner by immunostaining, fluorescent recovery after photobleaching, and biochemical analyses. Notably, translational pausing during XBP1u synthesis is indispensable for the recognition of HR2 by the signal recognition particle (SRP), resulting in efficient ER-specific targeting of the complex, similar to secretory protein targeting to the ER. On the ER, the XBP1u nascent chain is transferred from the SRP to the translocon; however, it cannot pass through the translocon or insert into the membrane. Therefore, our results support a noncanonical mechanism by which mRNA substrates are recruited to the ER for unconventional splicing.
巻・号 113(40)
ページ E5886-E5895
公開日 2016-10-4
DOI 10.1073/pnas.1604435113
PII 1604435113
PMID 27651490
PMC PMC5056097
MeSH Amino Acid Sequence Animals COS Cells Chlorocebus aethiops Endoplasmic Reticulum / metabolism* HEK293 Cells HeLa Cells Humans Intracellular Membranes / metabolism Models, Biological Nuclear Localization Signals / metabolism Protein Binding Protein Biosynthesis* Protein Transport RNA Splicing RNA, Messenger / genetics RNA, Messenger / metabolism Signal Recognition Particle / metabolism* Signal Transduction* X-Box Binding Protein 1 / chemistry X-Box Binding Protein 1 / genetics* X-Box Binding Protein 1 / metabolism
IF 9.412
引用数 17
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007) 293T(RCB2202)