A long way since the discovery of short RNAs

From Wightman, Ha, and Ruvkun, 1993

Since the turn of the current century, much attention has been focussed on microRNAs, a family of small, noncoding RNAs that have critical functions in regulating gene expression in development and disease. In a pair of papers published in Cell in late 1993, members of the Ambros and Ruvkun groups describe the interaction between the essential genes lin-4 and lin-14 in the worm Caenorhabditis elegans. Quite unexpectedly, lin-4 was found to be a small RNA that does not code for a protein product. Additionally, lin-4 was found to target lin-14 at the latter’s 3ʹ UTR, a region that had been thought of as bland and uninteresting. Despite their papers’ impact, the authors never set out to answer questions about noncoding RNAs or gene regulation. They simply wanted to know more about an interesting set of mutants. Perhaps that is what is so great about these experiments.

The papers:

• From the Ambros lab
• From the Ruvkun lab

Additionally, here are some reminiscences from the Ambros group and the Ruvkun group. They contain wonderful historical context, and some rather amusing anecdotes about the publication of these papers. A news and views article from Nature that was published about one month after the Cell papers provides some interesting insight into the reception of the groups’ work. There is clear excitement at the possibility of a new class of regulatory RNAs tempered by a dose of scepticism.