As can be seen from the figure, cell free RNA (cfRNA) is one of the earlier classes of ncRNA discovered (Szilágyi et al., 2020). cfRNA can be isolated from body fluids such as blood, urine, and cerebrospinal fluid (Stewart et al., 2018). Now the cfRNA has become an important tool in molecular biology and clinical research because it can provide information on gene expression, disease diagnosis, and treatment response. Before the 21st century, there were 33 different types of ncRNAs recorded in the literature, and 25 types of ncRNAs were newly discovered after 2000. Publications on rRNA, siRNA, miRNA, and tRNA are more extensive than other types of ncRNA, which may indicate that these RNA molecules have important regulatory functions. Furthermore, several kinds of ncRNAs have been studied for longer periods of time. tRNA and rRNA began to be studied relatively early, in 1959 and 1961 respectively (Smith et al, 1959; Aronson & McCarthy, 1961). The research directions of tRNA and rRNA include their structure, function, synthesis and regulation mechanism, etc. From its discovery to now, there are lots of researches to explore the possible association between tRNA and rRNA and diseases (Tuorto & Parlato, 2019).
In addition, publications on miRNAs and siRNAs have grown rapidly in the past few decades, even though they were discovered relatively late. miRNA and siRNA are two short-chain RNA molecules, both of which are non-coding RNAs, which play an important role in the RNA interference (RNAi) pathway (He & Hannon, 2004; Kurreck, 2009). These two RNA interference pathways are very important in the study of genetics, and are also research hotspots in recent years. Dysregulation of these two kinds of RNAs has been linked to the development and progression of various diseases. Besides, they have also been studied extensively in plants, where they play critical roles in plant development, stress responses, and defense against pathogens (Shukla et al., 2008).
New kinds of ncRNA molecules have been gradually discovered in recent years. For example, in 2010, researchers bidirectionally transcribed a new class of enhancer RNAs (eRNAs) within enhancer domains, and they observed that eRNA expression levels at neuronal enhancers were positively correlated with mRNA synthesis levels of nearby genes (Kim et al., 2010). In 2012, researchers discovered a class of small RNAs that play an important role in the repair of DNA double strand breaks (DSBs), and named them DSB-induced small RNAs (diRNAs) (Wei et al., 2012). In studying the development history of RNA, we will observe that the characteristics of many RNA species are similar. For example, lncRNAs include many RNA molecules with different functions. The newly proposed SPA lncRNA in 2016 is essentially a type of lncRNA. This is also one of the reasons why there are so many lncRNA publications so far (Wu et al., 2016). With the deepening of research, we will find more and more RNAs with different functions but similar structures, which may provide important ideas for subsequent RNA research.
