Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting.

Autor: Poulis P; Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Patel A; Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.; Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University of Göttingen, Göttingen, Germany., Rodnina MV; Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Adio S; Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University of Göttingen, Göttingen, Germany. sarah.adio@uni-goettingen.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 22; Vol. 13 (1), pp. 4231. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1038/s41467-022-31852-w
Abstrakt: When reading consecutive mRNA codons, ribosomes move by exactly one triplet at a time to synthesize a correct protein. Some mRNA tracks, called slippery sequences, are prone to ribosomal frameshifting, because the same tRNA can read both 0- and -1-frame codon. Using smFRET we show that during EF-G-catalyzed translocation on slippery sequences a fraction of ribosomes spontaneously switches from rapid, accurate translation to a slow, frameshifting-prone translocation mode where the movements of peptidyl- and deacylated tRNA become uncoupled. While deacylated tRNA translocates rapidly, pept-tRNA continues to fluctuate between chimeric and posttranslocation states, which slows down the re-locking of the small ribosomal subunit head domain. After rapid release of deacylated tRNA, pept-tRNA gains unconstrained access to the -1-frame triplet, resulting in slippage followed by recruitment of the -1-frame aa-tRNA into the A site. Our data show how altered choreography of tRNA and ribosome movements reduces the translation fidelity of ribosomes translocating in a slow mode.
(© 2022. The Author(s).)
Databáze: MEDLINE
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