Regulatory RNA molecules known as small regulatory RNAs are among the most exciting recent discoveries in gene regulation. They are of exceptional interest to biologists and drug researchers because their small size allows easy synthesis in the laboratory, and researchers can design their sequences to target transcripts of interest.

Two important types of small regulatory RNAs are known as siRNA (small interfering RNA) and miRNA (microRNA). While they have somewhat different functions, they share similarities in their production (Fig. 19.10). Both types of small RNA are transcribed from DNA and form hairpin structures, or stem-and-loops, stabilized by base pairing in the stem. Enzymes in the cytoplasm specifically recognize these structures and cleave the stem from the hairpin, then further cut the stem into small, double-stranded fragments 20–25 base pairs in length.

One of the two strands from each RNA fragment is incorporated into a protein complex known as RISC (RNA-induced silencing complex). The small, single-stranded RNA targets the RISC to specific RNA molecules by base pairing with short regions in the target. Depending on the type of small regulatory RNA, the RNA sequence in the RISC, and the particular type of RISC, the small regulatory RNA may result in chromatin remodeling, degradation of RNA transcripts, or inhibition of mRNA translation (Fig. 19.10). Other functions have also been reported.

Regulation by small RNAs is widespread in eukaryotes, and it is thought to have evolved originally as a defense against viruses and transposable elements. These molecules have also evolved to have important regulatory roles in their own right. Human chromosomes are thought to encode about 1000 microRNAs, each of which can target tens or hundreds of mRNA molecules. Half or more of human proteins may have their synthesis regulated in part by such small regulatory RNAs.

Quick Check 2 How do small regulatory RNAs differ from messenger RNA?