UNRAVELLING THE RNA REVOLUTION: A TIMELINE OF RNA BIOLOGY RESEARCH

Journal of Experimental Botany

By Pablo A. Manavella Instituto

Agrobiotecnología del Litoral, Santa Fe, Argentina, Editor.

Back in 1869, Friedrich Miescher discovered nucleic acids, which he called nuclein, in the kitchen of a monastery in Tübingen. Fifteen years later, Albrecht Kossel isolated the five nucleobases that shape DNA and RNA.

However, the nature and functions of RNA within living organisms were a complete mystery a century ago. Then, nearly 90 years ago, the role of RNA in protein synthesis was first suggested, a concept that was finally established in the 1950s. These discoveries boosted interest in these molecules, and many laboratories started paying attention to RNA. An avalanche of discoveries followed, including the discovery of the RNA synthesis process by Severo Ochoa; the deciphering of the genetic code and identification of tRNA by Marshall Nirenberg, Robert Holley and Har Gobind Khorana; and the discovery of introns and RNA splicing by Philip Sharp and Richard Roberts.

In the late 1960s and early 1970s, researchers began to explore the role of RNA in plants. As in humans, RNA molecules were shown to regulate gene expression in plants, either by directly binding to DNA or by interacting with other proteins or RNA molecules. Plant RNA research was behind that in animals, until the 1980s when Richard Jorgensen’s laboratory provided the first evidence of gene silencing. They showed that overexpressing the chalcone synthase gene in petunia resulted in flowers that were entirely or partially decoloured because both the transgene and the endogenous copy of the gene were silenced. However, the mechanism behind this result was unknown until studies in the late 1990s forged many concepts and mechanisms foundational to RNA interference. In particular, the work from David Baulcombe was seminal in our understanding of the principles behind RNAi and the identification of small interfering RNAs. Unfortunately, the Nobel committee ignored his fundamental contribution when the 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig Mello “for their discovery of RNA interference—gene silencing by doublestranded RNA”. This is perhaps one of the most notorious examples of “plant blindness”.

In any case, the discovery of RNAi opened up new avenues for studying gene function in plants, because researchers could now selectively “knock down” the expression of specific genes and study the effects on plant growth and development. It was a powerful tool that would transform the field of RNA biology in plants and many other organisms.