An RNAmazing 20 years

To the dismay of folks in my lab looking for shelf space for storage, I'm one of those PIs who has saved and treasured his copies of the RNA journal since Volume 1, Issue 1. However, let me put to rest the rumors that I used to read RNA articles to my son Jeremy at bedtime every evening. I never did such a thing in his formative years (he was old enough to read 'em himself….). Back in the infancy of this now well-established publication, I ran a joint RNA journal club with the Lutz lab in which we assigned journals to participants and would survey the field (and eat some delicious baked goods) every week. Being responsible for the RNA journal was both a joy and a curse as you always had interesting papers to present when an issue came out, but how could you chose which of the articles to focus on to summarize for the group? Congratulations to the RNA journal for 20 years of making journal clubs a great place to spend a Friday afternoon. Working in the RNA field has been quite an exciting ride over the last 20 years, hasn't it? A PubMed search using the term “DNA” shows that the number of indexed publications increased from 38,324 to 59,543 per calendar year since the RNA journal began in 1995, an increase of ∼55%. Publications that appear using the search term “RNA”, however, increased from 19,817 to 45,563 per calendar year—an increase of almost 130%. So despite major advances in DNA sequencing and genomics, one can use these stats to argue that our RNA field is expanding at more than twice the rate of the DNA field. There have been numerous significant advances in the realm of RNA biology over the last 20 years that have fueled this growth. These include the truly groundbreaking advances such as the discovery of RNA interference/the impact of small RNA regulators in cell biology, the discovery and characterization of riboswitches, major advances in elucidating RNA structures, and the determination of mechanisms and impact of regulated RNA processing and stability. Discoveries such as the growing impact of long non-coding RNAs, the networking of RNA-based processes and the rising role of RNA modifications in cell biology are also providing a vast amount of fuel to the field. The impact of the RNA biology that we know and love has also been compounded by a significant increase in its incorporation into many interdisciplinary arenas of investigation (e.g., stem cell biology, neuroscience, etc.). We've clearly forced many scientists (some kicking and screaming) to come out of their experimental comfort zone and enter the RNA realm in their research. What might the next 20 years have in store for the field of RNA Biology? Here's a list (in no particular order of priority) of questions that are among the key areas that need to be addressed in the field. (1) What is the function of the “dark matter” of the eukaryotic transcriptome? While significant work is already underway in this area, a thorough understanding of the biological functions of the plethora of non-coding transcripts has a very good chance of providing novel paradigms and groundbreaking innovation to our understanding of the molecular biology of the cell. (2) What are the components and dynamics of the messenger RNP? Our lack of understanding of what an mRNP truly consists of and how it dynamically changes through the life of an mRNA is, in my opinion, a major rate limiting factor to future progress in the field. This is one of the key remaining frontiers in the study of fundamental aspects of gene expression. (3) What is the full range and relevance of RNA structures? RNA structure is an inherent part of all RNA biology, yet we still only have a rather rudimentary understanding of the forms assumed by most RNAs. Continued advancement in the area of RNA structural biology will undoubtedly deliver novel insights for both basic and applied science applications. (4) What is the role of higher order RNA-containing structures inside cells? We badly need to continue and expand work to generate an in-depth characterization of the array of RNA granules that form in cells during development and in response to a variety of external stimuli. These oftentimes elusive RNA structures undoubtedly play key roles in numerous aspects of cell biology and a better understanding of how and why they form should provide significant innovation. Improvements in single cell analyses should play a key role in this area (and several other areas on this list). (5) Are there additional significant nuances to how translation is regulated? While we clearly have a strong handle on the mechanistic basics of translation, my sense is that with so much cellular energy going into this process, the likelihood of additional regulation over and above what we are already aware of is high. The implications of ribosomal subpopulations, the continued expansion of the impact of different RBPs and RNA-mediators on translational efficiency, and the networking of translation with other processes also indicate that this field may be poised for some major breakthroughs. (6) What are the biological impacts of “social” RNA? Every living organism makes and secretes highly stable and effective RNases into the environment undoubtedly for reasons other than just to make our experimental lives frustrating at times. Thus understanding the impact of RNA-based intercellular and inter-organismal communication may prove extremely interesting. (7) What is the biological significance of regulatable RNA modification? Building off of recent work on the m6A modification of mRNA, future studies are likely to provide an exciting picture of the impact of RNA modifications on cell biology. (8) What is the ultimate role of RNA and post-transcriptional processes in the overall regulation of gene expression of complex cellular pathways? Understanding the molecular basis for eukaryotic RNA regulons may change our appreciation of the regulation of many key aspects of cell biology. (9) Does RNA biology play a more notable role in mechanisms of disease pathogenesis? In many cases, the molecular explanation of cytopathology and other pathological manifestations of viral diseases are not very well understood. As our understanding of the impact of RNA-based processes in cell biology increases, it would not surprise me if our understanding of pathogenic mechanisms increases as viruses disrupt the homeostasis of RNA/RBPs in the cell. (10) Can we generate game-changing RNA aptamers? I would be very surprised if RNA aptamer technologies did not advance to develop key reagents for basic research, diagnostic and therapeutic applications. This aspect of RNA biology should be a major player in synthetic biology in the coming years. Let me finish with some closing comments regarding the RNA journal. In this age of electronic publishing, we cannot understate the value and prestige of a Society-backed journal. The journal was established at a time when most biological scientists had just started to appreciate the nuances and potential impact of RNA-based regulation due to its interdisciplinary impacts. However without a journal that the field could call its own, RNA biology remained in many researchers’ minds as a footnote to DNA and protein-based processes rather than an independent, vibrant discipline. I have always felt that the RNA journal sets the benchmark for studies in RNA biology. As an editor for a review journal in the RNA field, frankly I use the RNA journal as the baseline to determine the activity in the field in order to put impact factors and other publication metrics into the appropriate perspective. I'd like to congratulate Tim, Ann Marie, the folks at CSHL Press and all of the RNA editors/editorial board past and present for a job well done. I would encourage everyone to buy these hard working individuals a beverage or two of their choice in Madison at the RNA Society Meeting this Spring. The journal's past is something to be extremely proud of and the future is brighter than a Spinach aptamer. The inane pun “you can't spell ‘jouRNAl’ without RNA” is actually a very true statement for this field.