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Ribosomal frameshifting may be controlled by mechanisms found in the mRNA sequence (cis-acting). This generally refers to a slippery sequence, an RNA secondary structure, or both. A −1 frameshift signal consists of both elements separated by a spacer region typically 5–9 nucleotides long. [ 2 ]
A slippery sequence is a small section of codon nucleotide sequences (usually UUUAAAC) that controls the rate and chance of ribosomal frameshifting. A slippery sequence causes a faster ribosomal transfer which in turn can cause the reading ribosome to "slip."
Translation can also be affected by ribosomal pausing, which can trigger endonucleolytic attack of the tRNA, a process termed mRNA no-go decay. Ribosomal pausing also aids co-translational folding of the nascent polypeptide on the ribosome, and delays protein translation while it is encoding tRNA. This can trigger ribosomal frameshifting. [8]
Nucleotides containing the genetic information are now on a single strand messenger template called mRNA. The mRNA is incorporated with a subunit of the ribosome and interacts with an rRNA. The genetic information carried in the codons of the mRNA are now read (decoded) by anticodons of the tRNA.
The HIV-1 ribosomal frameshift signal requires two cis-acting elements: a heptameric "slippery site" and a downstream secondary RNA structure separated by an 8-nucleotide spacer. [3] [4] The "Slippery Site" in HIV-1 is the heptamer 5'-U UUU UUA-3' (gag ORF indicated by the spaces), where frameshifting occurs.
In molecular cell biology the Insertion sequence IS1222 ribosomal frameshifting element is an RNA element found in the insertion sequence IS222. The ribosomal frameshifting element stimulates frameshifting which is known to be required for transposition .
The expression of ODC-AZ requires programmed, ribosomal frameshifting which is modulated according to the cellular concentration of polyamines. High levels of polyamines induce a +1 ribosomal frameshift in the translation of mRNA for the antizyme leading to the expression of a full-length protein .
The DnaX ribosomal frameshifting element is a RNA element found in the mRNA of the dnaX gene in E. coli. The dnaX gene has two encoded products, tau and gamma, which are produced in a 1:1 ratio. The gamma protein is synthesised due to programmed frameshifting and is shorter than tau.