Chapter 7: Noncoding RNAs
It was once believed that most genes encode proteins and most transcripts are messenger RNAs (mRNAs). According to some studies on the matter, the number of genes that do not encode proteins outnumbers those that do [63]. Unlike mRNAs, which are translated into proteins by the ribosome, these noncoding RNAs (ncRNAs) act functionally as an RNA transcript. NcRNAs that are greater than 200nt are called long noncoding RNAs (lncRNAs), and those that are less than 50nt can be called small noncoding RNAs (sncRNAs). The remaining intermediate size range from 50-199nt can be called short RNAs, although these exact length thresholds are a bit arbitrary.
7.1 Small Noncoding RNAs (srcRNAs)
As we learned in Chapter 6, the transcriptome includes small transcripts. These sncRNAs are involved in gene regulation and gene silencing, regulation of splicing, and possibly other epigenetic roles throughout the cell. Many sncRNAs act as guides to direct the sequence-specific activity of enzymes to other RNAs such as mRNAs or other transcripts. Other more recent studies have implicated sncRNAs in directing the binding to DNA through triplex interactions.
7.1.1 microRNAs
MicroRNAs (miRNAs, miRs) are small endogenous regulatory RNA molecules (18-25nt) that are involved in post-transcriptional gene silencing [64]. miRNAs are processed from longer primary transcripts. Hairpins are cut at the base by Drosha, producing a microRNA precursor (pre-miR). These hairpin precursors are shuttled out of the nucleus and cut at the loop to produce double-stranded RNA. Typically one of the products is incorporated into the RNA-induced silencing complex (RISC), and the other is degraded.
Target sites for microRNAs are in the 3′ UTR of protein coding genes, although they have been observed in protein-coding regions as well. The target sites are around 7 nt in length, complementary to positions 2-8 of the mature microRNA.
7.1.2 piRNAs
Piwi-interacting RNAs (piRNAs, piRs) are small endogenous RNAs molecules (21-31nt) that are part of the genome’s natural defense against transposons, and may be involved in post-transcriptional gene silencing and other epigenetic functions [65]. piRNAs are the most abundant class of small RNAs [66]. piRNAs are processed from longer primary transcripts based on complementary interactions with transposon transcripts. These small RNAs do not arise from hairpins, but rather the duplex interactions with the transposon transcripts. The enzymes Aubergene (Aub) and Argonaute 3 (Ago3) for processing [67]. Ago3 cuts the piRNA primary transcript by using a transposon-derived small RNA as a guide, and Aub cuts the transposon transcript using a mature piRNA as a guide.
7.1.3 Duplex RNA interactions
Many small RNAs function through the RNA duplex formation due to complementary sequence interactions. Let’s discuss how we can describe these types of interactions.
Consider the complementary RNA sequences [latex]A=\texttt{ACGCAUU}[/latex] and [latex]B=