TY - JOUR
T1 - Elongation Arrest by SecM via a Cascade of Ribosomal RNA Rearrangements
AU - Mitra, Kakoli
AU - Schaffitzel, Christiane
AU - Fabiola, Felcy
AU - Chapman, Michael S.
AU - Ban, Nenad
AU - Frank, Joachim
N1 - Funding Information:
We thank J. LeBarron for creating an RNA secondary structure display and analysis program. We thank R.A. Grassucci and G.S. Allen for preparing and imaging a high-Mg 2+ sample of a postinitiation ribosome complex, which was a kind gift from the laboratory of M. Ehrenberg. We thank M. Watters for assistance with the illustrations. This work was supported by HHMI, NSF DBI 9871347 and NIH grants R37 GM29169 and R01 GM 55440 (to J.F.) and P01 GM64676 (M.S.C. subcontract, T.A. Cross, PI). C.S. was supported by postdoctoral fellowships of the Roche Research Foundation and the Ernst Schering Research Foundation. The work was supported by the Swiss National Science Foundation (SNSF) (to N.B.), the NCCR Structural Biology program of the SNSF (to N.B.), and a Young Investigator grant from the Human Frontier Science Program (to N.B.). K.M. and F.F. (laboratories of J.F. and M.S.C., respectively) performed all of the analyses described in this paper as follows: K.M., cryo-EM image processing, atomic model generation and fitting, and data analysis and interpretation; F.F., refinement of atomic models into cryo-EM maps using RSRef.
PY - 2006/5/19
Y1 - 2006/5/19
N2 - In E. coli, the SecM nascent polypeptide causes elongation arrest, while interacting with 23S RNA bases A2058 and A749-753 in the exit tunnel of the large ribosomal subunit. We compared atomic models fitted by real-space refinement into cryo-electron microscopy reconstructions of a pretranslocational and SecM-stalled E. coli ribosome complex. A cascade of RNA rearrangements propagates from the exit tunnel throughout the large subunit, affecting intersubunit bridges and tRNA positions, which in turn reorient small subunit RNA elements. Elongation arrest could result from the inhibition of mRNA·(tRNAs) translocation, E site tRNA egress, and perhaps translation factor activation at the GTPase-associated center. Our study suggests that the specific secondary and tertiary arrangement of ribosomal RNA provides the basis for internal signal transduction within the ribosome. Thus, the ribosome may itself have the ability to regulate its progression through translation by modulating its structure and consequently its receptivity to activation by cofactors.
AB - In E. coli, the SecM nascent polypeptide causes elongation arrest, while interacting with 23S RNA bases A2058 and A749-753 in the exit tunnel of the large ribosomal subunit. We compared atomic models fitted by real-space refinement into cryo-electron microscopy reconstructions of a pretranslocational and SecM-stalled E. coli ribosome complex. A cascade of RNA rearrangements propagates from the exit tunnel throughout the large subunit, affecting intersubunit bridges and tRNA positions, which in turn reorient small subunit RNA elements. Elongation arrest could result from the inhibition of mRNA·(tRNAs) translocation, E site tRNA egress, and perhaps translation factor activation at the GTPase-associated center. Our study suggests that the specific secondary and tertiary arrangement of ribosomal RNA provides the basis for internal signal transduction within the ribosome. Thus, the ribosome may itself have the ability to regulate its progression through translation by modulating its structure and consequently its receptivity to activation by cofactors.
KW - RNA
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U2 - 10.1016/j.molcel.2006.05.003
DO - 10.1016/j.molcel.2006.05.003
M3 - Article
C2 - 16713583
AN - SCOPUS:33646524478
SN - 1097-2765
VL - 22
SP - 533
EP - 543
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -