Welcome to Silence

Abstract

Editorial Welcome to Silence [1], a new open-access journal devoted to RNA silencing and other pathways directed by non-coding RNAs. Silence springs from the extraordinary, yet brief, history of RNA silencing. In just two decades, we have seen the anomalous properties of plant and fungal transgenes connect with a series of amazing experiments in which injected double-stranded RNA triggered silencing in worms. These diverse lines of research revealed the essence of RNA interference (RNAi), and the importance of these discoveries has been recognized through numerous awards and accolades including a Nobel Prize for Fire and Mello [2,3]. Our current understanding of RNA silencing derives from experiments performed in organisms from three kingdoms, experiments that directly inspired billion-dollar investments by biotechnology and pharmaceutical companies to use RNA-silencing both to diagnose and to treat disease in humans. Both small interfering RNAs and microRNAblocking antisense oligonucleotides are now in human clinical trials [4]. Some of the first GM plants to be produced exploited RNA silencing, although the mechanisms were not well understood at the time [5,6]. The study of RNA silencing produced enabling technology that allows each gene in a sequenced genome--even cultured human cells--to be knocked out or knocked down, providing a lifeline to functional genomics. There can be no question that RNA silencing research has had an impact! RNA silencing has excited scientists and non-scientists alike: witness front-page headlines in the American and British press [7-10], even before the Nobel Prize. Such interest, of course, reflects the power of RNA silencing as biotechnology. But equally important is that RNA silencing exemplifies the elegant creativity of natural selection. Just as we might gaze in awe at a blue whale in the ocean (how can such a creature exist?), we marvel at the simple principles and complex molecular machines that underlie RNA silencing pathways. The role of silencing as an antiviral defence in plants and invertebrates illustrates this point: it uses the sequence of the invading virus itself to define the targets to be repressed and so has infinite specificity [11]. As a defense system RNA silencing is unsurpassed. The study of RNA silencing has now travelled far from its posttranscriptional roots. The link between RNA and epigenetic silencing by chromatin modification, for example, is well established in many organisms [12]. In other developments the discovery of novel families of small silencing RNAs continues to expand the universe of guides far beyond the original microRNA and small interfering RNA pioneers [13]. This diversity is not mere molecular icing on the RNAi cake, because silencing underpins biological phenomena as diverse as virus resistance, control of chromosome architecture, transposon activity, genome rearrangement, and development, as well as responses to biotic and abiotic stimuli [14]. In parallel, other types of RNA-mediated mechanisms have been discovered, from CRISP RNAs [15] in bacteria to unexpectedly large families of non-coding RNAs derived from the intergenic regions of animals and plants [16]. These discoveries have been informed by, and in turn enrich the intellectual framework of RNAi. Thus, Silence will enthusiastically publish papers on these and other RNAbased mechanisms in addition to studies of the canonical RNA silencing pathways. Papers with (RNA) AND (silence OR silencing) in their titles or abstracts first appeared in the mid 1990s; there are now more than 1,400 each year and the trend is increasing (source: Web of Science) [17]. So why introduce a new journal if these papers are already finding a home? Two answers explain our motivation in founding Silence. First, the history of silencing is one of extensive cross-fertilization among different research communities. Such interorganism as well as inter-disciplinary collaboration and discussion explains the remarkable productivity of our field. * Correspondence: phillip.zamore@umassmed.edu