Nature's Journal Club

David R. Liu

Harvard University, Cambridge, Massachusetts, USA

Thanks to the discovery of a new catalytic RNA, a chemical biologist can satisfy his student’s curiosity.

An first-year undergraduate recently asked me a remarkable question: are all natural ribozymes, RNA molecules with catalytic activity, simply leftovers from the ‘RNA world’? The RNA-world hypothesis supposes that RNA molecules were precursors to the first primitive forms of life, before the evolution of DNA and proteins.

Unanswered, my student’s question preoccupied me until I encountered a recent paper by Jack Szostak of Massachusetts General Hospital, Boston, and his co-workers (K. Salehi-Ashtiani et al. Science 313, 1788–1792; 2006).

Prior to this work, only two of the known natural ribozymes were associated with mammals. The rarity of catalytic RNAs in more recently evolved, higher-order cells could reflect their attrition on the evolutionary battlefield during the rise of more highly functional protein enzymes.

This paper, however, supports a different conclusion. Szostak’s group designed an ingenious system to isolate self-cleaving RNA molecules from RNA encoded in the human genome. Using this system, they discovered several new ribozymes.

One of these ribozymes, associated with a gene known as CPEB3, is highly conserved among placental mammals and marsupials, but is absent from non-mammalian vertebrates. This observation suggests that it arose relatively recently, around 200 million years ago.

We can therefore infer that some ribozymes have evolved in modern organisms, long after the era of the RNA world. The work elegantly demonstrates a new approach to the study of ancient molecules — and also reminds me that our youngest students can ask some of the best questions.

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