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Science 331 (6017): 586-589

Copyright © 2011 by the American Association for the Advancement of Science

Translational Pausing Ensures Membrane Targeting and Cytoplasmic Splicing of XBP1u mRNA

Kota Yanagitani, Yukio Kimata, Hiroshi Kadokura, Kenji Kohno*

Abstract: Upon endoplasmic reticulum (ER) stress, an endoribonuclease, inositol-requiring enzyme-1α, splices the precursor unspliced form of X-box–binding protein 1 messenger RNA (XBP1u mRNA) on the ER membrane to yield an active transcription factor (XBP1s), leading to the alleviation of the stress. The nascent peptide encoded by XBP1u mRNA drags the mRNA–ribosome–nascent chain (R-RNC) complex to the membrane for efficient cytoplasmic splicing. We found that translation of the XBP1u mRNA was briefly paused to stabilize the R-RNC complex. Mutational analysis of XBP1u revealed an evolutionarily conserved peptide module at the carboxyl terminus that was responsible for the translational pausing and was required for the efficient targeting and splicing of the XBP1u mRNA. Thus, translational pausing may be used for unexpectedly diverse cellular processes in mammalian cells.

Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan.

* To whom correspondence should be addressed. E-mail: kkouno{at}bs.naist.jp


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