The year 2019 marked the fortieth anniversary of the Chinese Society of Biochemistry and Molecular Biology (CSBMB), whose mission is to promote biomolecular research and education in China. The last 40 years have witnessed tremendous growth and achievements in biomolecular research by Chinese scientists and Essays in Biochemistry is delighted to publish this themed issue that focuses on exciting areas within RNA biology, with each review contributed by key experts from China.
An overview of RNA research in China has been well documented by Drs. Yuanchao Xue, Runsheng Chen, Lianghu Qu and Xiaofeng Cao  and Ling-Ling Chen . Chinese scientists are at the forefront of discoveries that have been acknowledged by the international research community. Currently, more than 200 independent research groups in China, situated mainly in Beijing, Shanghai, and other major cities, such as Hefei, Wuhan, Guangzhou, Hangzhou, and Shenzhen, focus on RNA-related research. A large proportion of these groups are led by principal investigators who earned their Ph.D. and/or postdoc outside of mainland China. Their experience and training obtained in the international research arena have aligned RNA research in China with global RNA research. High-quality international conferences in the field of RNA research are more regularly being held in China; for example, the Epigenetics and RNA meeting organized by Cold Spring Harbor Asia in Suzhou has become a popular destination for top researchers globally. The CSBMB has promoted RNA-related research and education in China. The last biennial meeting of the RNA Society of CSBMB in 2018 attracted more than 900 attendees, many of whom were Ph.D. students. The RNA Society of CSBMB also promoted a major research plan funded by National Natural Science Foundation of China, through which 101 RNA-related projects were funded with a total of 28.6 million US dollars over the past 6 years .
The textbook view of RNA often emphasizes its role as a messenger between DNA and protein, which is the key of the central dogma, a unified scheme proposed by Sir Francis Crick in the 1970s . Astonishingly, RNA has now been placed centerstage due to its roles beyond encoding proteins. Thanks to the success of international consortia such as the Human Genome Project, ENCODE, FANTOM, and EPIC [4,5] (EPIC Planning Committee, 2012; ENCODE Consortium, 2004) and contributions from many individual groups, it is now well recognized that the transcription is pervasive, meaning the majority of transcription events produce non-coding RNAs [5–9]. The biogenesis, function, and fate of these non-coding RNAs have become critical questions in the field.
This themed RNA issue contains several contributions that focus on long non-coding RNAs (lncRNAs). Dr. Runsheng Chen’s group, which has pioneered bioinformatics research of non-coding RNAs in China since the 1990s , summarizes the genetic variations associated with lncRNAs . One hotspot of RNA research in recent years concerns the biomolecular condensates that form through liquid–liquid phase separation or higher order interactions [11–13]. Dr. Ling-Ling Chen, an international leader in lncRNA research, summarizes together with co-author Yang Wang, the function and organization of one such condensate called paraspeckle within the nucleus, in which the NEAT1 lncRNA plays a fundamental role in paraspeckle organization . As reviewed by the authors, the development of imaging techniques such as Structured Illumination Microscopy has been critical for paraspeckle studies . Dr. Chen’s group have recently expanded the RNA imaging tool kit by developing CRISPR-Cas13-based system for visualizing RNAs dynamics in live cells, through which a kiss-and-run/fusion mode of paraspeckle dynamics was proposed . One abundant class of lncRNAs in mammalian cells is enhancer RNAs that are transcribed and associated with transcriptional enhancers [16,17]. In this issue, Dr. Yuanchao Xue and co-workers provide an overview of enhancer RNAs from their biogenesis, functions, and regulation, to their pathological significance . The same group recently elegantly described spatial RNA–RNA interactions among many lncRNAs, including enhancer RNAs and RNAs associated with promoters that form spatial interaction hubs, which could regulate transcription via chromosome looping . Another important class of molecules are RNA-binding proteins; RNAs are coated with proteins perhaps within seconds of their production . RNA-binding proteins are best known for their roles in RNA processing, such as RNA splicing  and 3′-end processing , whereas emerging evidence has demonstrated that they also associate with chromatin, especially around promoter regions [23,24], which links their roles to the regulation of transcription initiation and elongation. These functions are summarized by Dr. Rui Xiao, who together with Dr. Xiang-Dong Fu and co-workers, discovered widespread RNA-binding protein chromatin interactions in human cells .
The pervasive nature of transcription also places RNA fate determination and quality control in the spotlight [7,25,26]. Dr. Hong Cheng and co-worker Jianshu Wang elegantly review emerging evidence that RNA is already sorted during, or shortly after, transcription. This is partially attributed to a dynamic equilibrium of binding by different proteins ranging from RNA export factors to the nuclear RNA exosome and, as a result, RNA is exported to the cytosol, or is otherwise retained and/or degraded within the nucleus . As discovered by Dr. Cheng’s group, RNA sorting within the nucleus influences not only the RNA pool in the cytosol, but also feeds back to upstream transcription . Different RNA species in the cytosol are also tightly monitored and Dr. Hongwei Guo and co-workers provide an overview of RNA quality control in plants, and in particular, they describe how different species of small RNA mediate post-transcriptional gene silencing, a surveillance pathway that operates in tight cooperation with exonuclease-mediated RNA decay that regulates defense and development in plants . The same group recently reported an unexpected role for 22-nt siRNAs in mediating translational repression, specifically under stress conditions, exemplifying the diversity of small RNAs function in plant .
Indeed, small RNAs comprise an important class of non-coding RNAs whose regulatory roles have long been acknowledged. Together with co-workers, Dr. Xiaofeng Cao, a leading expert in plant epigenetics and RNA processing, review the biogenesis and functions of a class of germline-specific RNAs, phased small interfering RNAs (phasiRNAs) . They summarize how the presence of phasiRNAs exemplifies the complexity and integrity of RNA processing at different levels, and provide an overview of RNA processing in plants at the co- and post-transcriptional levels . As summarized by the authors, the complexity of RNA processing has started uncovering in plants. The group has shown recently that the residue G in poly(A) tail of mRNA can impact the binding of poly(A)-binding protein and translation efficiency . A classical class of small non-coding RNAs is represented by microRNAs, which play important roles in different aspects of gene expression, from transcription to RNA decay and translation. In this issue, Dr. Yangming Wang and co-workers review the current understanding of how microRNAs regulate the naïve-to-primed pluripotency transition in mammals .
RNA secondary structure affects every step of the RNA life cycle and is therefore of great interest and importance [34–36]. In this issue, Dr. Qiangfeng Cliff Zhang and co-worker Yanqiu Shao describe how RNA structure is related to human disease and outlines current progress in disease treatment and drug discovery through targeting RNA structure using small molecules . The secondary structure of RNAs is dictated not only by their primary sequence, but also by proteins that bind to them in vivo. In collaboration with Dr. Howard Chang’s group, Dr. Zhang’s group has mapped the in vivo RNA structure across mammalian subcellular compartments . The secondary structure of RNA can also be regulated by RNA modifications, which are often added co-transcriptionally [39,40]. Among the different RNA modifications, N6-methyladenosine (m6A) is one of the most abundant and extensively studied; nonetheless, the faithful detection of m6A can be challenging . In this issue, Dr. Guifang Jia and co-workers summarize the principles and uses of different m6A detection methods . The same group recently developed a chemical labeling-based and therefore antibody-free method for m6A detection .
We sincerely thank all the contributing authors of this special issue for their input. We believe that this issue presents aspects of RNA biology that would be of keen interest to scientists from broad backgrounds. Similar to many other areas of biology, RNA biology is progressing and expanding at an extremely rapid pace, in China and abroad, making it difficult to provide a generalized and unbiased summary. We are very much looking forward to seeing more discoveries on topics such as RNA- and protein-mediated biomolecular condensation, RNA fate determination and quality control, the role of lncRNAs and RNA-binding proteins in regulating transcription and the chromatin environment, RNA structure and modifications, and the roles of non-coding RNAs in regulating disease and development. These advances will surely emerge from the joint efforts of the entire international RNA research community. Due to space limitations of this issue and prior commitments of potential authors, we apologize that many aspects of RNA biology and perspectives of the field could not be included in this themed issue.
The author declares that there are no competing interests associated with the manuscript.
I would like to thank all the authors and external reviewers for their great contributions and input. I would also like to thank Professor Sir Peter Downes, President of the Biochemical Society, for the great discussions during his visit to the CSBMB annual meeting in 2019, from which the idea of this special issue was originated. Finally, I would like to thank the editorial team of Essays in Biochemistry, especially Emma Pettengale and Natalie Tawney for their great help in organizing this themed issue.