Abstract
Translation facilitates the transfer of the genetic information stored in the genome via messenger RNAs to a functional protein and is therefore one of the most fundamental cellular processes. Programmed ribosomal frameshifting is a ubiquitous alternative translation event that is extensively used by viruses to regulate gene expression from overlapping open reading frames in a controlled manner. Recent technical advances in the translation field enabled the identification of precise mechanisms as to how and when ribosomes change the reading frame on mRNAs containing cis-acting signals. Several studies began also to illustrate that trans-acting RNA modulators can adjust the timing and efficiency of frameshifting illuminating that frameshifting can be a dynamically regulated process in cells. Here, we intend to summarize these new findings and emphasize how it fits in our current understanding of PRF mechanisms as previously described.
Highlights
Protein synthesis is essential for any living cell
While there are numerous reviews which extensively detail general mechanisms and occurrences of recoding events, namely (Gesteland and Atkins, 1996; Ketteler, 2012; Caliskan et al, 2015; Atkins et al, 2016; Dever et al, 2018; Dinman, 2019b; Rodnina et al, 2020), in this review we focus mainly on PRF, where a different reading frame is accessed through controlled slippage of the ribosome on an mRNA (Figure 1)
The co-translational folding of the nascent polypeptide chain of the viral non-structural protein 10 (Nsp10) was determined to distinctly interact with the ribosomal tunnel resulting in an upregulated frameshifting level on SARS-CoV-2 mRNA (Bhatt et al, 2021)
Summary
Protein synthesis is essential for any living cell. Based on the genetic information encoded in the messenger RNA (mRNA) sequence, the ribosome catalyzes the peptide bond formation of each amino acid to the nascent polypeptide chain. Pausing at these sites likely opens a favorable time-window for codon-anticodon interactions to be re-established in the alternative reading frame, exactly which step of translation elongation is affected is still an open question.
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