Pausing Signals

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Science  29 Mar 2002:
Vol. 295, Issue 5564, pp. 2327-2329
DOI: 10.1126/science.295.5564.2327d

The curious story of tmRNA has taken an intriguing turn. When a translating ribosome reaches the end of an aberrantly truncated messenger RNA (mRNA), it stalls and becomes trapped, waiting in vain for the ribosome release factors that normally would be recruited by the stop codon. Enter tmRNA, which first binds to the ribosome (acting as a transfer RNA), and then encodes a short peptide segment (acting as a mRNA) that is attached to the end of the truncated protein and tags it for degradation by intracellular proteases. Hayes et al. have found that tmRNA also gets involved when the ribosome slows down as a consequence of encountering a rarely used arginine codon just in front of the stop codon. Apparently, this pause results in about 20% of correctly synthesized protein (in this instance, RbsK) being tagged and subsequently destroyed. How can this wastage be beneficial·

Nakatogawa and Ito, in a pair of papers examining the peculiar fate of the secretion monitor SecM, may have an answer. At first glance, it appears that SecM is made simply to be exported to the periplasm and degraded. A closer look has shown that a proline-containing segment near to the COOH-terminus of SecM interacts with the exit tunnel of the ribosome and serves to slow translation. This pause allows time for a secondary structural element encompassing the Shine-Dalgarno sequence in the SecA gene (which lies immediately downstream from the SecM gene) to unfold. Furthermore, this pause only transpires when there is not enough SecA protein to bind to the NH2-terminal portion of SecM, which acts to overcome the frictional pull of the exit tunnel. Thus, SecM regulates the cellular levels of SecA (which mediates general protein export to the periplasm) by signaling to the ribosome: If more SecA is needed, slow down so that the way ahead can be cleared of obstacles; if there is enough SecA, finish making SecM and do something else. The close spacing of bacterial genes—the start site of rbsR is just three nucleotides away from the end of rbsK— prompts the proposal that rare arginine codons may offer another mechanism for coordinate gene expression. — GJC

Proc. Natl. Acad. Sci. U.S.A.99, 3440 (2002); Cell108, 629 (2002); Mol. Cell7, 185 (2001).

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