Novel Insights in the Biogenesis of Small Regulatory RNAs

Small non-coding regulatory RNAs, in tandem with their effector proteins, have a profound impact on the post-transcriptional regulation of gene expression. Among them, microRNAs, siRNAs, and piRNA families all share 1) a series of sequential processing steps on a primary transcript to generate the mature functional species, and 2) they pair with a protein of the Argonaute family to exert their function. It is precisely this stereotypic processing and the interaction with effector proteins that distinguish small regulatory RNAs from random RNA degradation products. However, whilst the core catalytic steps are well known, alternative processing pathways expand the spectrum of RNA species that can produce small regulatory RNAs. Moreover, epitranscriptomic modifications of RNA, A-to-I editing, and non-templated nucleotide additions to the precursor RNAs add additional regulatory layers to the small RNA biogenesis and function.

microRNAs are processed by the sequential cleavage of a hairpin embedded in a primary transcript by two RNaseIII enzymes, Drosha and Dicer. However, over the years there is mounting evidence of how non-canonical processing steps can by-pass these committed steps or provide an entry point to the microRNA processing pathway for other small RNA species. Moreover, editing and other RNA modifications can enhance or impair miRNA processing. Sub-optimal microRNA precursors may rely on base editing or non-templated nucleotide addition that improves their biogenesis, while in other instances these modifications can block processing entirely. Overall, these additional steps offer a unique opportunity to add new layers of regulation to the microRNA processing and activity. In turn, these novel processing mechanisms can be harnessed to develop new small regulatory RNAs with improved activities for potential clinical use. 

In this Research Topic, we want to explore novel insights and recent advances on the processing and regulation of small regulatory RNAs, including microRNAs, siRNAs, piRNAs, snoRNAs, among others. In particular, we are interested in, but not limited to, the following:

• Novel insights into small RNA processing pathways

• Regulation of small RNA processing pathways

• Editing and modification of small RNAs

• Applications of non-canonical small RNA processing pathways in therapeutics.

• Synthetic RNA modifications to enhance small RNA activity and stability.