4.3 Hairpin formation and micro-RNAs
A class of small RNA molecules called micro-RNAs (miRNAs) has been identified in recent years. The roles of these small RNAs are only just beginning to be understood, but many are expressed only at specific developmental stages. Indeed, the first observations of miRNAs were made in C. elegans because of their mutant developmental phenotypes. The genes that encode these miRNAs are called mir genes (pronounced ‘meer’) and have now been identified within the genomes of various animals and plants. Many of the genes are evolutionarily conserved for sections of their sequence and all are inverted repeat sequences.
What can you predict about the structure of the mRNA synthesized from mir genes, assuming the rules of maximum base pairing?
As the mir genes are inverted repeats, the mRNA will also contain an inverted repeat. The most likely structure to form will be a hairpin, as this will provide maximum pairing of the bases.
The hairpin structures are believed to be a critical part of miRNA function, as they are found in a divergent range of organisms. Shown in Figure 19 are miRNAs encoded by a gene called mir-1. The predicted structures of the hairpins of the mir-1 miRNAs from C. elegans, D. melanogaster and human reveal that each is capable of forming into a hairpin chain. In most cases, the stem of the hairpin contains several mismatched bases, although the majority are perfectly matched.
MiRNA molecules are processed by a protein complex containing a ribonuclease called dicer, to produce small RNA chains that are between 21 and 25 nucleotides in length. Highlighted within each hairpin in Figure 19a is the small 21-nucleotide product RNA that is produced from each of these precursor miRNAs. Note that the base sequence of this 21-nucleotide RNA is identical between these three organisms.
These small RNAs derived from miRNAs by the action of dicer appear to exert their cellular effect through base-pairing interactions with other target nucleic acids; presumably the specificity of base pairing serves a role in the recognition of these targets. Most is known about their influence on the stability or translation of target mRNAs that contain a complementary sequence of bases. MiRNAs have also been implicated in alterations in chromatin structure. Mir genes are believed to be numerous in most eukaryotic genomes; for example, it is estimated that the human genome contains 250 mir genes.