Beyond the Central Dogma

The central dogma of molecular biology explains that DNA codes for RNA, which codes for proteins. InThe Central Dogma, you can learn about the important roles of messenger RNA, transfer RNA and ribosomal RNA in the protein-building process. But RNA does more than just build proteins. RNA has many jobs in the cell, including jobs that have been traditionally associated with DNA and proteins. Read on to learn about how RNA can carry hereditary information, act as enzymes, and fine-tune protein production. And learn how advances in RNA technology are helping investigators study genes, as well as diagnose and treat diseases.

Most organisms use DNA to store genetic information. The DNA passes from parents to offspring over generations. But some viruses, including HIV, the virus that causes AIDS, use RNA to carry genetic information. RNA viruses are known as retroviruses.

RNA has a structure similar to DNA's; in both molecules, the sequence of bases can code for proteins. RNA was likely the molecule of heredity in some of the earliest life forms.

Enzymes are catalysts: they build and break down molecules at a rate quick enough to sustain life. Scientists used to think that all enzymes in the cell were proteins. Then it was discovered that some RNA molecules can be enzymes too. So-called ribozymes are rare, but they play key roles in the cell. In the ribosome, RNA joins amino acids together, allowing cells to build proteins. Some mRNA molecules contain self-splicing introns, which can break and rejoin the mRNA strand. And a ribozyme in the RNAse P complex activates tRNA molecules by clipping off their ends.

Ribozymes provide further evidence that RNA may have been the first molecule of life. In a primitive life form, RNA may have both catalyzed chemical reactions and stored genetic information, functions that were later taken over by DNA and proteins.

Some RNA molecules can silence specific genes, turning off the production of proteins that are not needed at a certain place or time. This job is especially important during development, when cells begin to differentiate into specific types, such as muscle, skin, and liver. Each cell type needs only a fraction of its total genes to be active in order to do its job.

Gene-silencing RNA molecules recognize specific genetic sequences through complementary base-pairing. These RNA molecules can shut down portions of the genome, turning off protein production. RNA does this by recruiting proteins to modify histones (or the epigenome). Modified histones wrap DNA tightly, making it inaccessible to transcription machinery.

RNA interference. Scientists can use the cell's gene-silencing machinery to study genes. First, they build a small RNA molecule with a nucleotide sequence that matches a specific gene. When the RNA is injected into an embryo, it finds the gene and turns it off permanently so that no protein is made from it. By looking at what happens as the organism develops without the gene, scientists learn something about the gene's natural function.

RNA interference is a natural process that cells evolved to destroy RNA-based viruses. Cellular machinery identifies and cuts double-stranded RNA molecules (1). Then it uses the fragments to find longer complementary RNA strands (3), which it then destroys.

Some RNAs silence harmful DNA sequences that sit in our genomes as relics of our evolutionary past. Transposons ("jumping genes") and the genes of infecting viruses made their way into our ancestors' DNA, and they continue to be passed from parent to offspring. RNAs inactivate viral genes and transposons, keeping them from harming us.

A variety of RNA molecules help the cell to fine-tune when, where, and how much of a particular mRNA molecule, and by extension a particular protein, is made. Regulatory RNAs can act on just about every step of the protein-production process. Some RNAs (called riboregulators) bind DNA switches to turn genes on and off. Others interact directly with mRNA molecules to alter splicing, protect mRNA from harm, or cut it to pieces.

Riboswitches help some cells respond to an external signal, usually a small molecule. Riboswitches are found on large mRNA molecules, and they fold into intricate shapes. When the small molecule—such as a metal ion, amino acid, or nucleic acid—binds to the riboswitch, it causes the shape of the RNA to change. The shape change affects whether or not the mRNA is translated into protein.

In bacteria, riboswitches regulate mRNAs that code for proteins involved in metabolic pathways. The small molecule that triggers the riboswitch is typically part of the same pathway. So the riboswitch provides feedback to the pathway.

Scientists are building RNA molecules and using them as tools to diagnose and even treat diseases, including cancer, diabetes, arthritis, heart disease, brain diseases, and viral infections.

Scientists can easily design RNA molecules that will attach to a specific nucleotide sequence in a gene or mRNA molecule. These RNA molecules could someday be used to inactivate a broken disease gene. As a diagnostic tool, RNA molecules can be designed to identify certain substances in the blood that are only present with a certain disease.

Misbehaving RNA molecules can also cause diseases, such as Alzheimer's and other neurodegenerative diseases. The more we learn about RNA's role in these diseases, the more prepared we will be to treat them.