Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting
2022 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Poulis, Panagiotis; Patel, Anoshi; Rodnina, Marina V. ; Adio, Sarah
- Abstract
- 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.
- Issue Date
- 2022
- Journal
- Nature Communications
- Organization
- Max-Planck-Institut für Multidisziplinäre Naturwissenschaften ; Institut für Mikrobiologie und Genetik ; Abteilung Molekulare Strukturbiologie
- eISSN
- 2041-1723
- Language
- English
- Sponsor
- Open-Access-Publikationsfonds 2022