Time for a Pause

Science Signaling  08 Feb 2011:
Vol. 4, Issue 159, pp. ec41
DOI: 10.1126/scisignal.4159ec41

In metazoan cells, accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR) in which unconventional splicing of a precursor form of XBP1 (XBP1u) messenger RNA (mRNA) by an ER membrane protein, IRE1, results in the formation of mature XBP1s mRNA. The XBP1s mRNA encodes a functional transcription factor that induces the expression of the ER resident molecular chaperones to alleviate the stressful situation. The nascent XBP1u peptide recruits the mRNA–ribosome–nascent chain (R-RNC) complex to the ER membrane. Yanagitani et al. (see the Perspective by Ron and Ito) now report that translation of XBP1u mRNA is transiently paused near the 3′ end of its open reading frame to stabilize the R-RNC complex. Mutational analysis of XBP1u revealed an evolutionarily conserved peptide module at the C-terminal region responsible for translational pausing, which was required for the efficient ER-targeting and splicing of the XBP1u mRNA. Thus, regulation of translational speed using a module embedded inside a protein promotes targeting of its mRNA for efficient splicing.

K. Yanagitani, Y. Kimata, H. Kadokura, K. Kohno, Translational pausing ensures membrane targeting and cytoplasmic splicing of XBP1u mRNA. Science 331, 586–589 (2011). [Abstract] [Full Text]

D. Ron, K. Ito, A translational pause to localize. Science 331, 543–544 (2011). [Abstract] [Full Text]