Translational Pausing Ensures Membrane Targeting and Cytoplasmic Splicing of XBP1u mRNA

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Science  13 Jan 2011:
DOI: 10.1126/science.1197142


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 membrane for the efficient cytoplasmic splicing. Here, we find that translation of the XBP1u mRNA is transiently 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.