Messenger RNA (mRNA) can lose its stop codon as a result of damage. Ribosomes that translate damaged mRNA into proteins do not release the incomplete protein. The protein remains attached to the ribosome and which have fatal consequences. In such cases, bacterial cells direct the ribosome to a special sort of RNA. This transfer-messenger RNA, tmRNA, recognises the snarled-up ribosome and designates the protein produced as waste. The ribosome is released and the failed protein is then destroyed to prevent it from causing damage. Sharief Barends discovered that the protein SmpB (Small protein B) modified the structure of the tmRNA so that it is available for repair work sooner. SmpB is also essential for transporting tmRNA to the area where the problem is located.
The problem solver tmRNA consists of two parts. The 't' (transfer) part directs the snarled-up ribosomes to the 'm' (messenger) area. This 'm' part of the tmRNA contains a stop codon which completes the unfinished translation so that the ribosome can release the protein. The 'm' part also sends a signal to the failed protein that it must be broken down.
The 't' part of this problem solver differs from normal tRNA. Both tRNA and tmRNA are created from the shortening and maturation of a longer precursory RNA molecule. However, the normal tRNA is created much more quickly than its more complex brother and binds to a transport protein much more strongly. The biochemist discovered that the addition of SmpB speeded up the development of tmRNA into an adult problem solver. The protein alters the three-dimensional structure of the 't' part. The molecule is more similar to normal tRNA and as a result of this is available for repair work sooner. It also binds more strongly to EF-Tu, a protein responsible for the transport to snarled-up ribosomes.
Finally, Barends discovered that a certain plant virus uses the repair principle of tmRNA. The mRNA of turnip yellow mosaic virus (TYMV) carries a disguised tRNA at its terminus, which is very similar to the tRNAs of the host cell. A host ribosome 'thinks' that this is its own tRNA, draws the disguised tRNA in and starts to produce viral proteins. The virus is reproduced and the host cell succumbs. Barends published the discovery of this deception, similar to that of the Trojan horse, in the journal Cell last January.
For further information please contact Dr Sharief Barends (Leiden University, now working at IBMC du CNRS, Strasbourg), tel. 33-388-417048, e-mail: barends@chem.leidenuniv.nl. or assistant supervisor Dr Barend Kraal, tel. 31-715-274-770, e-mail: b.kraal@chem.leidenuniv.nl. The doctoral thesis was defended on 8 May 2003. Dr Barends' supervisor was Prof. C.W.A. Pleij.
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The research was funded by the Netherlands Organisation for Scientific Research.