RNA Made Easy: Structure, Function & Role in Biology

Ribonucleic acid (RNA full form) is a polymeric molecule that plays a variety of roles in biology, including gene coding, decoding, control, and expression. Ribonucleic acid (RNA) is a vital biological macromolecule found in all living organisms. Nucleic acids include RNA and deoxyribonucleic acid (DNA). Nucleic acids are one of the four primary macromolecules required for the functioning, survival and existence of  all known forms of life, in addition to lipids, proteins, and carbohydrates. 

More About RNA

RNA, like the DNA, is made up of a number of nucleotides in a chain, but unlike DNA, it is generally found in nature as a single strand folded over itself rather than a paired double strand. Messenger RNA (mRNA full form) guides the synthesis of certain proteins by conveying genetic information, using the nitrogenous bases of guanine, uracil, adenine, and cytosine, indicated by the letters G, U, A, and C. An RNA genome is used by many viruses for encoding their genetic information.

Within the cells, certain RNA molecules are used to catalyse biological activities, govern and regulate gene expression, and sense and communicate responses in the form of cellular signals. Protein synthesis, in which RNA molecules control the production of proteins on ribosomes, is one of such active processes. Transfer RNA (tRNA) molecules shuttle amino acids to the ribosome, where ribosomal RNA (rRNA) joins amino acids to generate coded proteins.

DNA and RNA

RNA has a molecular structure that is very much similar to DNA, yet it varies in three major ways: 

• In many of its own biological functions, RNA is a single-stranded molecule with far shorter chains of nucleotides as compared to the double-stranded DNA. Intrastrand double helixes can be formed by complementary base pairing in a single RNA molecule, the most common example is  tRNA. 

• Deoxyribose is found in the sugar-phosphate "backbone" of DNA, whereas ribose is found in RNA. In the 2' position of the pentose ring, ribose possesses a hydroxyl group, but in contrast to DNA deoxyribose does not. By decreasing the activation energy of hydrolysis reaction, the hydroxyl groups present in the ribose backbone make RNA more chemically labile in comparison to DNA.

• In DNA, thymine is the complementary nucleotide to adenine, but in RNA uracil is an unmethylated version of thymine.

Self-complementary sequences in most physiologically active RNAs, such as mRNA, tRNA, rRNA, snRNAs and other non-coding RNAs, allow sections of the RNA to fold and mate with itself to create double helices, similar to DNA. The highly organised nature of these RNAs has been discovered through analysis. Unlike DNA, they don't have lengthy double helices in their structures; instead, they have collections of small helices packed together in protein-like structures.

RNAs can produce chemical catalysis like enzymes. The structure of the ribosome - which is a huge RNA-protein complex that catalyses the synthesis of peptide bonds - for example, revealed that its active site is entirely made up of RNA.

The Structure of RNA

A ribose sugar is found in each nucleotide of RNA, with carbons numbered 1' through 5'. Adenine (A), cytosine (C), guanine (G), or uracil (U) are the bases connected to the 1' position (U). Purines are adenine and guanine, whereas pyrimidines are cytosine and uracil. The 3' position of one ribose and the 5' position of the next both have phosphate groups connected to them. Because each of the phosphate groups has a negative charge, RNA is a charged molecule (polyanion). Between cytosine and guanine, adenine and uracil, and guanine and uracil, the bases create hydrogen bonds. Other interactions are conceivable, such as the GNRA tetraloop, which has a guanine–adenine base pair, or a collection of adenine bases attaching to each other in a bulge.

The presence of a hydroxyl group at the 2' position of the ribose sugar is a key structural feature of RNA that separates it from DNA. The presence of this functional group leads the helix to mainly adopt the A-form geometry, while RNA can occasionally adopt the B-form in single strand dinucleotide situations. The A-form geometry produces a major groove that is very deep and narrow, and a minor groove that is shallow and broad. A second effect of the presence of the 2'-hydroxyl group is that it can chemically attack the neighbouring phosphodiester bond to break the backbone in conformationally flexible sections of an RNA molecule that are not involved in the creation of a double helix.

Although RNA is transcribed with only four bases - adenine, cytosine, guanine, and uracil, these bases and the sugars connected to them can be altered in a variety of ways as the RNA matures. Pseudouridine, in which the C–N bond between uracil and ribose is replaced with a C–C bond, and ribothymidine (T) can be found in a variety of locations (the most noteworthy being the T–C loop of tRNA). Hypoxanthine, a deaminated adenine base with the nucleotide inosine, is another important modified base (I). The amino acid inosine is important in the wobble theory of the genetic code.

There are about 100 additional modified nucleosides found in nature. tRNA has the highest structural diversity of modifications, but pseudouridine and nucleosides with 2'-O-methyl ribose, which are commonly found in rRNA, are the most prevalent. The precise roles of many of these RNA alterations are yet unknown. Many of the post-transcriptional alterations in ribosomal RNA, however, occur in highly functional areas like the peptidyl transferase centre and the subunit interface, showing that they are crucial for proper operation.

Single-stranded RNA molecules, like proteins, typically require a certain tertiary structure to operate. Secondary structural components, such as hydrogen bonds inside the molecule, provide the framework for this structure. Hairpin loops, bulges, and internal loops are some of the recognizable "domains" of secondary structure that result from this. Two or three bases are insufficient to build an RNA for any given secondary structure, while four bases are sufficient. This is why nature "selected" a four-base alphabet: anything less than four does not allow for the creation of all structures, and anything more than four is unnecessary. Metal ions, such as Mg²+, are required to stabilize many secondary and tertiary structures because RNA is charged.

D-RNA, which is made up of D-ribonucleotides, is the naturally occurring enantiomer of RNA. The D-ribose contains all of the chirality centers. L-RNA can be synthesized using L-ribose or rather L-ribonucleotides. L-RNA is substantially more resistant to RNase destruction. A folded RNA molecule's topology, like that of other organized bio-polymers like proteins, may be defined. This is frequently done using circuit topology, which is the configuration of intra-chain connections within a folded RNA.

The Production of RNA 

Transcription is the main process of synthesizing RNA using DNA as a template, which is generally done by an enzyme called RNA polymerase. The binding action of the enzyme to a promoter region in the DNA is the first step in the transcription process (usually found "upstream" of a gene). The helicase activity of the enzyme unwinds the DNA double helix. The enzyme then proceeds in a 3' to 5' direction along the template strand, creating a corresponding RNA molecule with elongation in the 5' to 3' direction. The DNA sequence also determines where RNA production will come to an end.

After transcription, enzymes frequently modify RNAs. The spliceosome, for example, adds a poly(A) tail and a 5' cap to eukaryotic pre-mRNA and removes introns. 

A variety of RNA-dependent RNA polymerases use RNA as a template for the synthesis of a new strand of RNA. This sort of enzyme is used by a variety of RNA viruses (such as the poliovirus) to replicate their genetic material. In many species, RNA-dependent RNA polymerase is also a member of the RNA interference pathway.

Contribution of RNA Research

Many key biological discoveries and Nobel Prizes have resulted from RNA research. Friedrich Miescher discovered nucleic acids in 1868 and named the substance 'nuclein' since it was found in the nucleus. The presence of nucleic acids in prokaryotic cells, which lack a nucleus, was subsequently revealed. In 1939, it was suspected that RNA played a role in protein synthesis. Severo Ochoa and Arthur Kornberg earned the Nobel Prize in Medicine in 1959 for discovering an enzyme that can manufacture RNA in the lab.