UNRAVELLING THE RNA REVOLUTION: A TIMELINE OF RNA BIOLOGY RESEARCH

Journal of Experimental Botany

By Pablo A. Manavella Instituto de 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.

It was also the gateway to studying the molecular basis of epigenetics, especially in plants, where small RNAs are central actors.

Within the last decades, and assisted by the advance of sequencing technologies, we have identified many different RNA molecules with essential roles in plants and other organisms. Groundbreaking discoveries in the RNA biology field have included the development of RNA-mediated gene editing, the therapeutic usages of mRNAs and our current advances in understanding the mechanisms behind epigenetics and the importance of non-coding genomic regions. Plant biologists have made tremendous contributions in this work. This year, the Journal of Experimental Botany and The Plant Cell published RNA biology special issues reviewing many aspects of this exciting field and future perspectives in this area.1,2 As RNA biologists, we are aware of many compelling open questions to tackle in the near future.3 These will only scratch the surface of what is hidden behind, and there is still much to learn about RNA biology’s complex and fascinating world and how RNA biology can help people, plants and our planet.

References:

1. Marquardt S, Manavella PA. A ribose world: current status and future challenges of plant RNA biology. J Exp Bot 2023; 74: 2203–2207.

2. Eckardt NA, Axtell MJ, Barta A, et al. Focus on RNA biology. Plant Cell 2023; in press.

3. Manavella PA, Herz MAG, Kornblihtt AR, et al. Beyond transcription: compelling open questions in plant RNA biology. Plant Cell 2022; in press.