key: cord-0010363-nmn41dh5
authors: Cattaneo, Roberto
title: How ‘hidden’ reading frames are expressed
date: 2003-03-21
journal: Trends Biochem Sci
DOI: 10.1016/0968-0004(89)90266-1
sha: 7b35987f1cba85fb42310e37e1bb705b99e558c7
doc_id: 10363
cord_uid: nmn41dh5

Secondary reading frames, ‘hidden’ under other reading frames, are used for coordinated expression of proteins in several eukaryotic viruses. In some genes, ribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are translational mechanisms allowing access to such ‘hidden’ reading frames. In others, secondary reading frames are translated from alternatively spliced or edited mRNAs.

Secondary reading frames, 'hidden' under other reading frames, are used ]br The use of an internal AUG codon coordinated expression of prgteins in several eukaryotic viruses. In some genes, for initiation of translation is an alternribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are tra.~slational mechanisms allowing access to such 'hid-ative to ribosomal frameshifting, and den' reading flames. In others, secondary reading flames are translated from does not result in production of fusion alternatively spliced or editedmRNAs, proteins ( Fig. 1 , bottom center, black box). Several conditions may allow the use of an internal AUG codon. (1) An Eukaryotic mRNAs are generally codon, only one protein will be internal AUG is sometimes used in monocistronic, but for sev,zral viral expressed (bottom left, stippled box). cases wherc the first AUG occurs in an transcripts ~-s as well as for orLe cellular Ribosomal frameshifting, subsequent unfavourable context for translation transcript 9, it has been shown that pro-to initiation on the first AUG codon, initiation 4. (2) Termination of protein teins encoded in different reading may enable expression of the overlap-synthesis at a stop codon may lead to frames are expressed. Since eukaryotic ping reading frame, creating a fusion reinitiation at a nearby AUG in ribosomes typically start protein syn-protein (bottom right, fused stippled another frame ~12. (3) A 'ribosome thesis at the first AUG codon only 4, it is and black boxes). Since only a fraction landing pad' may direct the ribosome to not immediately evident how second-of the ribosomes change frame at a an internal position in the mRNA, as ary reading frames overlapping with or frameshift signal, fusion proteins are described for the uncapped genomic following the first reading frame can be produced in addition to, rather than RNA of picornaviruses ~3. (4) In a capexpressed, instead of, the 'normal' protein, ped mRNA of a paramyxovirus, some Frameshifting in the -1 frame is ribosomes pass from the cap directly to Ribosomal frameshifting used by most retroviruses to access the an initiation codon far downstream14. A situation present in many viral reverse transcriptasc reading frame 5"~', It is interesting to note that the eukaryotic transcripts is illu~,trated in hidden in the gag mRNA, and by cousins of rctroviruses and the yeast Ty Fig. 1 region is extensively altered by insertion of one or more U residues at 121 transcriptase 8"15. Even more intrigu-lation, i.e. 'stuttering' of the pol-sites and by deletion of Us at seven ingly, ribosomes can use ACG orAUA ymerase. This enzyme is believed to sites 2s. Moreover, mRNAs coding for for initiation on the HBV reverse tran-stutter at the end of each gene on short very similar proteins are expressed in scriptase reading frame, albeit at con-stretches of template U residues to three species of trypanosomes which siderably reduced efficiency s. This is polyadenylate viral mRNAs.

In carry remarkably different genes in reminiscent of a trick used by the 20-50% of the phosphoprotein their mitochondrial genomes >. These adeno-associated virus (a parvovirus) mRNAs of SV5 (Ref. 20) and measles two last observations have been chaland Sendai virus (a paramyxovirus) to virus 21, nontemplated G residues are lenged by Maizels and Weiner 3°, who initiate protein synthesis with different inserted at a precise position, probably have postulated the existence of an efficiency on ACG or AUG codons in by means of intragenic polymerase RNA template or of a nuclear gene the same mRNA ~<17.

stuttering on a stretch of templated Cs. coding for these mRNAs. Portable ribosomal frameshifting The protein products of the viral type signals (~, as well as portable ribosome of RNA editing are fusion proteins 'Hidden' reading frames in eellular landing pads 13, have been defined and (Fig. 1, right) . As with ribosomal genes? used to study the expression of foreign frameshifting (which also produces Ribosomal frameshifting, internal proteinslS. These tools can now be used fusion proteins), viral RNA editing initiation of protein synthesis, and experimentally to co-ordinate expres-does not act on all template molecules, RNA editing are frequently used in sion ofspecificproteins, and allows coordinated expression of viral systems to allow the expression of two types of proteins. 'hidden' reading frames. In contrast, in Viral RNA editing: reading frame cellular genes overlapping reading switch Cellular RNA editing: new stop eodon frames are present only rarely, and to In other viral and cellular eukaryotic or alteration of the reading frame my knowledge none has been shown to genes, secondary reading frames are Cellular types of RNA editing seem code for an expressed protein. In cellutranslated from alternatively spliced or to be mechanistically unrelated to the lar genes of higher eukaryotes, coordiedited mRNAs. As alternative splicing as an expression mechanism has been Tablel. Three types of RNA editing reviewed recently ~9, I will concentrate Site(s), frequency and Consequences for on RNA editing. The three different Gene and organism Type of modification Base other characteristics protein expression forms of RNA editing (Table I) will contain an article

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