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Ribosomal frameshift
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Ribosomal frameshift

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Ribosomal frameshift AI simulator

(@Ribosomal frameshift_simulator)

Ribosomal frameshift

Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can be programmed by the nucleotide sequence of the mRNA and is sometimes affected by the secondary, 3-dimensional mRNA structure. It has been described mainly in viruses (especially retroviruses), retrotransposons and bacterial insertion elements, and also in some cellular genes.

Small molecules, proteins, and nucleic acids have also been found to stimulate levels of frameshifting. In December 2023, it was reported that in vitro-transcribed (IVT) mRNAs in response to BNT162b2 (Pfizer–BioNTech) anti-COVID-19 vaccine caused ribosomal frameshifting.

Proteins are translated by reading tri-nucleotides on the mRNA strand, also known as codons, from one end of the mRNA to the other (from the 5' to the 3' end) starting with the amino acid methionine as the start (initiation) codon AUG. Each codon is translated into a single amino acid. The code itself is considered degenerate, meaning that a particular amino acid can be specified by more than one codon. However, a shift of any number of nucleotides that is not divisible by 3 in the reading frame will cause subsequent codons to be read differently. This effectively changes the ribosomal reading frame.

In this example, the following sentence of three-letter words makes sense when read from the beginning:

However, if the reading frame is shifted by one letter to between the T and H of the first word (effectively a +1 frameshift when considering the 0 position to be the initial position of T),

then the sentence reads differently, making no sense.

In this example, the following sequence is a region of the human mitochondrial genome with the two overlapping genes MT-ATP8 and MT-ATP6. When read from the beginning, these codons make sense to a ribosome and can be translated into amino acids (AA) under the vertebrate mitochondrial code:

However, let's change the reading frame by starting one nucleotide downstream (effectively a "+1 frameshift" when considering the 0 position to be the initial position of A):

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