Molecular Genetics 

Facts

• In Mo-MuLV RNA (and the RNAs of other type C retroviruses),
• gag and pol are in the same reading frame but separated by a termination codon.
• Translation of the pol cistron is accomplished by suppression by a gln tRNA.
• Reverse transcriptase, the product of the pol portion of the gene binds the translation termination factor eRF1, thus inactivating it.
• Similarly, the RNA of tobacco mosaic virus (and other tobamoviruses) contains a suppressible stop codon. The read through product contains the RNA polymerase domain.
• Reverse genetic experiments using reporter genes for the downstream coding regions, reveal that regions both upstream and downstream of the suppressible stop codon are required for suppression.  Regions downstream seem more conserved than those upstream (ref).

Interpretations

• Termination suppression has the same effect as frameshifting: the production of two proteins, one longer than the other.
• Retroviruses have evolved strategies to accelerate their replication by a feed forward regulation mechanism of translation (ref).
• Sequence context determines whether suppression occurs at a given stop codon. A complex signal prevents normal stop codons from being suppressed.
• The efficiency of termination suppression determines the stoichiometric ratio of the longer to the shorter product.

Further information

• Termination suppression, though often seen in translation of viral mRNAs and mRNAs transcribed from transposable elements, is not a frequent event in mRNA expression by translation.  Non-viral mRNAs for which some evidence suggests that read-through is part of its normal translation are:
• the gag-pro gene of the Skipper element of Dictyostelium discoide\um (ref)
• the trachea branching developmental gene hdc of Drosophila (ref)
• the Kelch gene of Drosophila (ref)
• A variety of amino acids can be incorporated in response to read-through termination codons (ref).
• Although first thought to occur by direct termination suppression, the translation of the full length RF2 protein is now known to occur by regulated frameshifting.
• Sequences in the immediate downstream region have been classified into three (ref) or six (ref) groups based on sequence.

This is page 2423 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 2000, 2002, 2004