RNA

Ribonucleic acid (abbreviated RNA) is a nucleic acid present in all living cells that has structural similarities to DNA.[1] Ribonucleic acid (RNA) is an essential molecule that performs many roles in the cell, from carrying the instructions to make proteins to regulating genes.[2] Unlike DNA, however, RNA is most often single-stranded. An RNA molecule has a backbone made of alternating phosphate groups and the sugar ribose, rather than the deoxyribose found in DNA.[1]

Chemical Structure and Composition

It is made up of nucleotides, which are ribose sugars attached to nitrogenous bases and phosphate groups.[3] Attached to each sugar is one of four bases: adenine (A), uracil (U), cytosine (C) or guanine (G).[1] The nitrogenous bases in RNA are adenine, guanine, cytosine, and uracil, which replaces thymine in DNA.[5]

The ribose sugar of RNA is a cyclical structure consisting of five carbons and one oxygen. The presence of a chemically reactive hydroxyl (−OH) group attached to the second carbon group in the ribose sugar molecule makes RNA prone to hydrolysis.[5] This chemical lability of RNA, compared with DNA, which does not have a reactive −OH group in the same position on the sugar moiety (deoxyribose), is thought to be one reason why DNA evolved to be the preferred carrier of genetic information in most organisms.[5]

Types of RNA

Different types of RNA exist in cells: messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA).[1] Of the many types of RNA, the three most well-known and most commonly studied are messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), which are present in all organisms.[5]

Messenger RNA (mRNA)

In protein synthesis, mRNA carries genetic codes from the DNA in the nucleus to ribosomes, the sites of protein translation in the cytoplasm.[5] Because mRNAs carry the instructions or "code" for making proteins, they are referred to as coding RNA.[2] Once a ribosome binds to an mRNA transcript, it starts decoding the mRNA codons and recruits tRNAs with the encoded amino acid. Codons are deciphered using the genetic code. In the genetic code, each codon represents a specific amino acid—for example, CUU codes for leucine, and GGU codes for glycine.[3]

Ribosomal RNA (rRNA)

rRNAs combine with proteins to create the structure of the ribosome. As ribosomes read the instructions encoded in the mRNAs, the rRNAs perform the chemical reactions that assemble the new proteins piece-by-piece.[2] For this reason, rRNAs make up about 80-90% of all the RNA in a human cell.[2] The RNA portion of at least one cellular RNP has been shown to act as a biological catalyst, a function previously ascribed only to proteins.[5]

Transfer RNA (tRNA)

Transfer RNAs, called tRNAs for short, assist in translation. Each tRNA corresponds to one of the 20 possible protein building blocks in humans. These building blocks are known as amino acids. As the ribosome reads each codon along an mRNA, the tRNA bring the correct amino acid, which is then added to the growing protein molecule.[2] tRNAs are folded into a distinct L-shape that helps them carry out their function. One end of the tRNA has a specific sequence to match a codon on the mRNA, while the other end of the tRNA has a site to carry the amino acid that will be added to the new protein.[2]

Non-coding RNA

All other types of RNA are called noncoding RNA. There are many types of noncoding RNAs with many different functions.[2] Another group of RNAs regulate the activity of genes. These regulatory RNAs can bind to DNA or other RNAs (or even proteins) to influence how a gene is expressed.[2]

RNA Structure and Folding

Unlike its double-stranded cousin deoxyribonucleic acid, which twists into a double-helix structure, RNA folds and bonds to itself. Because the three-dimensional structure into which RNA folds determines its cellular function, scientists are very interested in understanding how it folds.[4] Many types of RNA, including tRNAs, fold into specific shapes that help them function and keep them stable. Complementary sequences at different positions along the length of an RNA fold the molecule into loops and other complex structures.[2]

However, the presence of self-complementary sequences in the RNA strand leads to intrachain base-pairing and folding of the ribonucleotide chain into complex structural forms consisting of bulges and helices. The three-dimensional structure of RNA is critical to its stability and function, allowing the ribose sugar and the nitrogenous bases to be modified in numerous different ways by cellular enzymes that attach chemical groups (e.g., methyl groups) to the chain. Such modifications enable the formation of chemical bonds between distant regions in the RNA strand, leading to complex contortions in the RNA chain, which further stabilizes the RNA structure.[5]

Ribozymes and Catalytic Functions

Some RNAs also function as catalytic RNA to drive biochemical reactions; hence they are termed ribozymes. The ribozymes also sometimes pair with auxiliary proteins to carry out their catalytic functions. The biochemical reactions catalyzed by ribozymes include protein synthesis, RNA splicing, and RNA cleavage.[3] Additionally, RNA has been found to possess catalytic properties, leading to the discovery of ribozymes, which are RNA molecules that can act as enzymes.[9]

Ribozymes classify into two types: small ribozymes (eg- hairpin, hammerhead, and Hepatitis delta virus) and large ribozymes (group I and II introns, RNase P, spliceosome, and the ribosomes).[3]

RNA in Gene Regulation

MicroRNA and Small Interfering RNA

The microRNA (miRNA) is a form of small, single-stranded RNA, 18–25 nucleotides long. It is transcribed from DNA, instead of being translated into protein, and regulates the functions of other genes in protein synthesis. Therefore, miRNAs are genes that modulate other protein-coding genes.[21]

The major difference between siRNAs and miRNAs is that the former inhibit the expression of one specific target mRNA while the latter regulate the expression of multiple mRNAs.[22] Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing.[27]

RNA Splicing

Small nuclear RNAs (snRNA) are non-coding RNAs that are responsible for splicing introns. The snRNAs join with proteins to form small nuclear ribonucleoproteins (snRNP), which most commonly contain U1, U2, U4, U5, and U6 snRNA molecules.[3] siRNAs targeting intronic or exonic sequences close to an alternative exon regulate the splicing of that exon.[24]

RNA Synthesis and Processing

Transcription is the process of RNA formation from DNA, and translation is the process of protein synthesis from RNA.[3] RNA is synthesized from DNA by an enzyme known as RNA polymerase during a process called transcription. The new RNA sequences are complementary to their DNA template, rather than being identical copies of the template.[7]

RNA molecules of all types are continually being synthesized and degraded in a cell; even the longest-lasting ones exist for only a day or two. Shortly after the structure of DNA was established, it became clear that RNA was synthesized using a DNA molecule as a template, and the mechanism was worked out shortly thereafter. The entire process by which an RNA molecule is constructed using the information in DNA is called transcription. An enzyme called RNA polymerase is responsible for assembling the ribonucleotides of a new RNA complementary to a specific DNA segment (gene).[9]

RNA Viruses

Certain viruses use RNA as their genomic material.[1] An RNA virus uses RNA instead of DNA as its genetic material and can cause many human diseases.[3] There are different kinds of RNA viruses, and each has a unique mechanism of replication. Double-stranded RNA viruses, such as retroviruses, fuse with host cell membranes and inject their viral contents inside to replicate their genome via reverse transcription.[3]

RNA World Hypothesis

All RNA World hypotheses include three basic assumptions: (1) At some time in the evolution of life, genetic continuity was assured by the replication of RNA; (2) Watson-Crick base-pairing was the key to replication; (3) genetically encoded proteins were not involved as catalysts. The general notion of an "RNA World" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts.[11]

According to the RNA World Hypothesis, around 4 billion years ago, RNA was the primary living substance, largely due to RNA's ability to function as both genes and enzymes.[13] According to this hypothesis, RNA stored both genetic information and catalyzed the chemical reactions in primitive cells.[12]

There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous.[11] The discovery of ribozymes supported the RNA World Hypothesis. The strongest argument for proving the hypothesis is perhaps that the ribosome, which assembles proteins, is itself a ribozyme. Despite the fact that the ribosome is composed of both RNA and protein, the processes involved in translation are not catalyzed by protein, but by RNA, indicating that early life forms may have used RNA to catalyze chemical reactions before they used proteins.[13]

Biological Significance

The functions of RNA are broad and include carrying biological information, providing structure, facilitating chemical reactions and regulating the functions of DNA and other RNA molecules.[2] These and other types of RNAs primarily carry out biochemical reactions, similar to enzymes. Some, however, also have complex regulatory functions in cells. Owing to their involvement in many regulatory processes, to their abundance, and to their diverse functions, RNAs play important roles in both normal cellular processes and diseases.[5]

Besides the most important function of RNA to make proteins, other critical cellular functions include modifying and restructuring other RNAs and regulating gene expressions during growth and development, and changing cellular environments.[3]