MicroRNAs: An exciting and open field calls for extensive study from initial and established investigators

摘要

It was not until the year 1998 that the Nobel Prize-winning discovery of RNA interference (RNAi) by Fire and Mello with their colleagues initiated the study of the expansive world of small RNAs. The discovery of short/small interfering RNAs (siRNAs) based on works from several pioneers, including Hannon, Zamore, Tuschl, Baulcombe, and their colleagues, further opened a big window for small RNAs. Shortly afterward, the hunt for various kinds of endogenous small RNAs by several leading investigators, including Bartel, Ambros, and their colleagues, led to the recognition of a large family of endogenous small RNAs, namely microRNAs (miRNAs). lin-4 and let-7, discovered by Ambros and colleagues in 1993 and by Ruvkun and colleagues in 2000, respectively, are the two founding members of this big family. MiRNAs are small RNAs, only 21-25 nucleotides (nt); most of them are hidden in the neglected non-protein-coding regions of the genome and are widespread in plants and animals. Thousands of miRNAs have been identified, and many are highly conserved within the animal or the plant kingdoms but divergent between the two kingdoms. While siRNAs target mRNAs mainly for destruction, miRNAs regulate mRNAs through either destroying the targets or repressing the translation of the target RNAs (cover figure). The major difference between siRNA and miRNA in mammals is that the former targets very specific mRNAs that are fully complementary to the siRNAs for destruction, while the latter broadly targets many different mRNAs that are only partially complementary to the 5' region of the miRNA. As a consequence, a miRNA has the potential to target hundreds of mRNAs, and many biological processes are thus potentially under the control of miRNAs.