What's in the name? That which we call a rose by any other name would smell as sweet.

de Breyne, Sylvain, Nathalie Chamond, Didier Décimo, Mary-Anne Trabaud, Patrice Andre, Bruno Sargueil, and Théophile Ohlmann. 2012. “In Vitro Studies Reveal That Different Modes of Initiation on HIV-1 mRNA Have Different Levels of Requirement for eIF4F.” The FEBS Journal (July 3). doi:10.1111/j.1742-4658.2012.08689.x.

What I would like to say about this manuscript is that it has nothing to do with HIV-1 mRNA translation. It's just irrelevant and reproduces old data. Bold statement indeed, but I'll try to convince you. What do the authors think they study? HIV-1 translation. As far as I know, there exists a set of HIV-1 mRNAs, all of them possessing 5'UTRs (1). However, the authors continue to use an artificial mRNA without any 5'UTR, thereby strating directly with gag AUG-codon. Somehow they do not bother if this is physiologically relevant or no. So shall we.

Prior to reading this manuscript I highly recommend reading two undeservedly forgotten researches, which were remotely mentioned by the authors. Here they are: (2) and (3). In the former translation of an artificial mRNA with two separated AUG-codons was studied in RRL. And the latter research deals with a behavior of leaderless mRNA in RRL.

Testing different concentrations of an mRNA with 5'UTR and two AUG codons.

de Breyne et al., Figure 1B: increasing mRNA (HIV1 5'UTR-AUG1-AUG2) concentration in RRL results in a continuous increase of initiation frequency at the second AUG codon and, starting from a certain concentration, decrease in initiation frequency at the first AUG codon.

Dasso et al., Figure 4A: increasing mRNA concentration (irrelevant 5'UTR-AUG1-AUG2) in RRL results in a continuous increase of initiation frequency at the second AUG codon and, starting from a certain concentration, decrease in initiation frequency at the first AUG codon.

Addition of a competitor to an mRNA with 5'UTR and two AUG codons.

de Breyne et al., Figure 1C: addition of a competitor (HIV-1 5'UTR) results in an increase of initiation frequency at the second AUG.
Dasso et al., Figure 5: addition of a competitor (E.coli 16S rRNA) results in an increase of initiation frequency at the second AUG.

Effect of 5'-terminal m7G-cap on AUG1 and AUG2

de Breyne et al., Figure 2 and S2: capping simulates translation at AUG1 and does not affect initiation at AUG2.
Dasso et al., Figure 7: initiation frequency at AUG2 is not affected by mRNA capping

Requirements for eIF4A

de Breyne et al., Figure 4: eIF4A R362Q mutant does not inhibit translation initiation at AUG1 of leaderless mRNA
Andreev et al., Figure 3: 48S complex is efficiently formed on the leaderless mRNA in the absence of eIF4F or eIF4A.

In the absence of proper control (any other mRNA with two AUG codons or any other leaderless mRNA which both would behave essentially similar to the corresponding mRNAs used in this study) all the authors say is totally irrelevant to HIV-1. And, sadly, there is nothing new in these data. Is a corpus of published papers so huge that those referees have forgotten these papers (2,3) or are they just unfamiliar with them?

1. Yilmaz, Alper, Cheryl Bolinger, and Kathleen Boris-Lawrie. 2006. “Retrovirus Translation Initiation: Issues and Hypotheses Derived From Study of HIV-1..” Current HIV Research 4 (2): 131–139.

2. Dasso, M C, S C Milburn, J W Hershey, and R J Jackson. 1990. “Selection of the 5'-Proximal Translation Initiation Site Is Influenced by mRNA and eIF-2 Concentrations.” European Journal of Biochemistry / FEBS 187 (2): 361–371.

3. Andreev, Dmitri E, Ilya M Terenin, Yan E Dunaevsky, Sergei E Dmitriev, and Ivan N Shatsky. 2006. “A Leaderless mRNA Can Bind to Mammalian 80S Ribosomes and Direct Polypeptide Synthesis in the Absence of Translation Initiation Factors.” Molecular and Cellular Biology 26 (8): 3164–3169.