The central dogma of molecular biology suggests that DNA contains the information to code for all of our proteins, and three different types of RNA translate this code into polypeptides rather passively. In particular, messenger RNA (mRNA) carries the protein blueprint from the cell's DNA to its ribosomes, which are the "machines" that control protein synthesis. The RNA (tRNA) then transfers the appropriate amino acids to the ribosome for incorporation into a new protein. Meanwhile, the ribosomes themselves are made up primarily of ribosomal RNA (rRNA) molecules.
However, in the half century since the structure of DNA was first developed, scientists have learned that RNA plays a much larger role than just participating in protein synthesis. For example, many types of RNA have been found to be catalytic, meaning they carry out biochemical reactions in the same way that enzymes do. In addition, many other RNA species have been found to play complex regulatory roles incells.
Thus, RNA molecules play multiple roles in both normal cellular processes and disease states. Usually those RNA molecules that do not take the form of mRNA are called non-coding because they do not code for proteins. Participation of non-coding mRNAs in many regulatory processes. Their prevalence and diversity of functions led to the hypothesis that the "RNA world" could precede the evolution of DNA and RNA functions in the cell, participation in protein biosynthesis.
Non-coding RNAs in eukaryotes
There are several varieties of non-coding RNA in eukaryotes. Most notably, they transfer RNA (tRNA) and ribosomal RNA (rRNA). As mentioned earlier, both tRNA and rRNA play an important role in the translation of mRNA into proteins. For example, Francis Crick suggested the existence of adapter RNA molecules that could bind to the mRNA nucleotide code, thereby facilitating the transfer of amino acids into growing polypeptide chains.
The work of Hoagland et al. (1958) indeed confirmed that a certain fraction of cellular RNA was covalently linked to amino acids. Later, the fact that rRNA turned out to be a structural component of ribosomes suggested that, like tRNA, rRNA also does not code.
In addition to rRNA and tRNA, there are a number of other non-coding RNAs in eukaryotic cells. These molecules assist in many of the important energy-storing functions of RNA in the cell, which are still enumerated and defined. These RNAs are often referred to as small regulatory RNAs (sRNAs).in eukaryotes, they have been further classified into a number of subcategories. Together, regulatory RNAs exert their effects through a combination of complementary base pairing, complexation with proteins, and their own enzymatic activity.
Small nuclear RNA
One important subcategory of small regulatory RNAs consists of molecules known as small nuclear RNAs (snRNAs). These molecules play an important role in the regulation of genes through RNA splicing. SnRNAs are found in the nucleus and are usually tightly associated with proteins in complexes called snRNPs (small nuclear ribonucleoproteins, sometimes referred to as "snurps"). The most common of these molecules are the U1, U2, U5, and U4/U6 particles, which are involved in pre-mRNA splicing to form mature mRNA.
MicroRNA
Another topic of great interest to researchers is microRNAs (miRNAs), which are small regulatory RNAs approximately 22 to 26 nucleotides in length. The existence of miRNAs and their contractile RNA functions in the cell in gene regulation were originally discovered in the nematode C. elegans (Lee et al., 1993; Wightman et al., 1993). Since their discovery of miRNAs, they have been identified in many other species, including flies, mice, and humans. So far, several hundred miRNAs have been identified. There may be many more (He & Hannon, 2004).
MiRNAs have been shown to inhibit gene expression by repressing translation. For example, miRNAs encoded by C. elegans, lin-4 and let-7,bind to the 3'-untranslated region of their mRNA targets, preventing the formation of functional proteins at certain stages of larval development. So far, most miRNAs studied appear to control gene expression by binding to target mRNAs through imperfect base pairing and subsequent inhibition of translation, although some exceptions have been noted.
Additional research shows miRNAs also play an important role in cancer and other diseases. For example, the miR-155 species is enriched in B cells derived from Burkitt's lymphoma, and its sequence also correlates with a known chromosomal translocation (exchange of DNA between chromosomes).
Small interfering RNA
Small interfering RNA (siRNA) is another class of RNA. Although these molecules are only 21 to 25 base pairs long, they also work to silence gene expression. In particular, one strand of a double-stranded siRNA molecule can be included in a complex called RISC. This RNA-containing complex can then inhibit the transcription of an mRNA molecule that has a complementary sequence to its RNA component.
MiRNAs were first identified by their involvement in RNA interference (RNAi). They may have evolved as a defense mechanism against double-stranded RNA viruses. SiRNAs are derived from longer transcripts in a process similar to that by which miRNAs occur and processing of both types of RNA involves the same enzymeDicer. The two classes appear to differ in their repression mechanisms, but exceptions have been found in which siRNAs exhibit behaviors more typical of miRNAs and vice versa (He & Hannon, 2004).
Small Nucleolar RNA
Within the eukaryotic nucleus, the nucleolus is the structure in which rRNA processing and ribosomal assembly take place. Molecules called small nucleolar RNAs (snoRNAs) have been isolated from nucleolar extracts due to their abundance in this structure. These molecules function to process rRNA molecules, which often results in methylation and pseudouridylation of specific nucleosides. Modifications are mediated by one of two classes of snoRNAs: C/D-box or H/ACA-box families, which typically involve the addition of methyl groups or uradine isomerization in immature rRNA molecules, respectively.
Non-coding RNAs in prokaryotes
However, eukaryotes have not driven the market into non-coding RNAs with specific regulatory energy functions of RNAs in the cell. Bacteria also possess a class of small regulatory RNAs. Bacterial rRNAs are involved in processes ranging from virulence to the transition from growth to stationary phase that occurs when a bacterium is faced with a nutrient deprivation situation.
One example of bacterial rRNA is the 6S RNA found in Escherichia coli. This molecule has been well characterized, with its initial sequencing occurring in 1980. 6S RNAis conserved across many bacterial species, indicating an important role in gene regulation.
RNA has been shown to affect the activity of RNA polymerase (RNAP), the molecule that transcribes messenger RNA from DNA. 6S RNA inhibits this activity by binding to a polymerase subunit that stimulates transcription during growth. Through this mechanism, 6S RNA inhibits the expression of genes that stimulate active growth and helps cells enter the stationary phase (Jabri, 2005).
Riboswitches
Gene regulation - in both prokaryotes and eukaryotes - is influenced by RNA regulatory elements called riboswitches (or RNA switches). Riboswitches are RNA sensors that detect and respond to environmental or metabolic signals and thus influence gene expression.
A simple example of this group is the temperature sensor RNA found in the virulence genes of the bacterial pathogen Listeria monocytogenes. When this bacterium enters the host, the elevated temperature inside the host's body melts the secondary structure of the segment in the 5' untranslated region of the mRNA produced by the bacterial prfA gene. As a result, changes occur in the secondary structure.
Additional riboswitches have been shown to respond to heat and cold shocks in a variety of organisms and also regulate the synthesis of metabolites such as sugars and amino acids. Although riboswitches appear to be more common in prokaryotes, many have also been found in eukaryotic cells.
