**2. History of non-coding RNA**

The beginning of the era of RNA dates back to the discovery of nucleic acids by Friedrich Miescher in the late 1860s. Later on, rigorous research was carried out about its structure, mode of action, and expression. Soon it became clear that majorly three kinds of RNA were involved in the protein production process, translation where mRNA was the carrier of genetic information ultimately translated into protein, and the process is assisted by tRNA and rRNA. Secondly, with the advent of newer technologies in molecular biology, several new RNA molecules appeared in the picture, out of which some had some role in the regulatory pathways or physiological pathways, for some other function is still unknown. Since, among all these only, mRNA codes for the protein, all other RNAs are termed non-coding RNA.

The first non-coding RNA to be discovered was the tRNA and its role in transferring amino acids was first observed by Paul C Zamecnik and Mahlon Hoagland in a cell-free system when RNA molecules were radioactively labeled [7]. Furthermore, it was the first non-coding RNA to be sequenced [8]. Later, in the early twenty-first century, many types of non-coding RNA, such as siRNA, miRNA, and piRNA, were discovered namely which had a role in gene regulation. During post-transcriptional gene silencing, a 25-nucleotide antisense RNA complementary to the target RNA was detected. This short interfering RNA, in virus-induced gene silencing, suppresses the production of viral proteins on binding with the target viral mRNA. This is a type of defense mechanism based on RNA against RNA and DNA viruses [9].

*Caenorhabditis elegans* is a completely sequenced nematode used as a model organism for many research programs. Out of its four larval stages, L1, L2, L3, and L4, it was found that the gene lin-4, the first miRNA discovered, was crucial for the transition of the larva from L1 to L2 [10].

H19 and Enod40 were the first eukaryotic lncRNA to be discovered [11]. The first plant lncRNA was discovered by Crespi in 1994. Long non-coding RNAs were first described during the whole genome sequencing and several types of lncRNA, such as Xist, Airn, MALATI, HOTAIR were discovered [12]. **Table 1** summarizes the different discovery events of the ncRNAs.
