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

Poulis, P., Patel, A., Rodnina, M. V., & Adio, S. (2022). Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting. Nature Communications, 13: 4231. doi:10.1038/s41467-022-31852-w.

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Poulis, P.1, Author           
Patel, A.1, Author           
Rodnina, M. V.1, Author           
Adio, S., Author
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1Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350156              

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 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.

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Language(s): eng - English
 Dates: 2022-07-22
 Publication Status: Published online
 Pages: 15
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-022-31852-w
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Title: Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 13 Sequence Number: 4231 Start / End Page: - Identifier: ISSN: 2041-1723