RNA was once relegated to a subsidiary role in biochemistry apparently dominated by DNA as the genetic material and proteins as the workhorse molecules. In recent years, however, biologists have discovered many new and surprising functions of RNA molecules.
In a typical Biology 101 course, we are told that RNA has three primary roles--as ribosomal RNA, messenger RNA, and as transfer RNA--all of which are involved with protein synthesis. Not so long ago this was the sum total of knowledge regarding RNA's role in the biochemistry of the cell. As early as 1967, however, Francis Crick and Leslie Orgel had suggested that RNA might serve as a catalyst like protein enzymes, since RNA can form similar complex three-dimensional structures. Indeed, it turned out that peptide bonds are formed in the RNA core of the ribosome without the aid of protein co-factors. The demonstration of other catalytic abilities of RNA led to the concept of a primordial RNA world (previously discussed in our Scientia blog) wherein RNA was the predominant macromolecule. Even in the today's world, the role of RNA in the cell is surprisingly complex and seems to be still evolving.
RNA that cleaves RNA
In 1982, Thomas Cech showed that a primary RNA transcript from Tetrahymena could splice itself, without the aid of proteins.It has been subsequently shown that group I and group II introns, in general, are capable of self-splicing. The former appear to be an example of selfish DNA that jumps from gene to gene and even across species, using an RNA intermediate. Cech shared the 1989 Nobel prize for chemistry with Sidney Altman, who demonstrated that RNA sub-unit of RNAse P was responsible for cleaving off the 5' leader sequences of precursor tRNAs.
RNA as a template
Retroviruses, like HIV, use their genomic RNA as a template from which to synthesize DNA using reverse transcriptase. A ubiquitous eukaryotic cellular gene, telomerase, is also a reverse transcriptase. It employs a small RNA sub-unit as a template to synthesize the DNA repeats found on the ends of chromosomes. A complementary 'guide RNA' is also used as a template during some types of mRNA editing, a process wherein the message is altered after transcription.
A riboswitch is an RNA molecule that alters the activity of a gene by binding small molecules. For instance, the glycine riboswitch alters the activity of genes involved in glycine metabolism. Typically, riboswitches are cis-acting elements found in the untranslated regions of mRNAs. Upon binding their ligand, they may induce transcriptional termination or cleave themselves or, in some cases, alter the splicing pattern of the transcript. Some riboswitches also act in trans to regulate transcription of genes of which they are not a part.
RNAi (inhibitory RNA)
The RNAi gene silencing system is found only in eucaryotes. It involves the production of small interfering RNA (siRNA) transcripts, typically of 20-15 bases, which are complementary to specific mRNAs. These anneal and the resulting double stranded sequence is cut by the argonaute enzyme of the RNA-induced silencing complex (RISC). A related system involves genomically encoded micro RNAs that anneal imperfectly, and may inhibit multiple mRNA species.
A more recent RNA innovation is the Xist transcript, which is necessary for X chromosome inactivation in mammals. Mammalian females have two X chromosomes, whereas males have only one. In order to maintain the correct gene dosage, one of the female's X chromosomes is maintained as inactive heterochromatin. The Xist RNA transcript is encoded by the X chromosome and is processed like a mRNA but does not code for a protein. Instead the transcripts bind in multiple locations to one of the X chromosomes, and in cooperation with nuclear proteins, keep the chromosome in an inactive state.
Though the primordial 'RNA World' has receded into history, the very versatile RNA macromolecule keeps finding new functional niches as evolution proceeds.