Structural Biochemistry/Nucleic Acid/RNA

RNA is also known as ribonucleic acid. It is a part of most living organisms as well as viruses. It contains bases of Adenine, Cytosine, Guanine, and Uracil (instead of Thymine) which all bind to the ribose. RNA can be used to make DNA as well as synthesize proteins. It is the only polymer that can serve as a catalyst to the formation of proteins as well as storing genetic information. The RNA backbone is made of alternating ribose-phosphate groups. RNA can be found usually single stranded in humans, but can appear double stranded in many other organisms, including viruses.

Some viruses have RNA as their primary genetic material. They are known as RNA viruses. These viruses infect cells by first binding to a specific protein or receptor on the surface of the cell. After binding to the cell's surface, the virus injects its genetic material, or RNA, into the cell. The viral RNA, then, associates with the ribosomes of the infected cell. Essentially, a virus seizes control of its host's molecular machinery, uses the host cell's transcriptional abilities to produce viral proteins. The newly-made viral proteins then go on to produce new viruses. Furthermore, viral RNA can form replication complexes where it can copy itself. This newly-replicated RNA then gets packaged into the newly created viruses, which leads the cell to lyse, or break open. Consequently, these released viruses can go on to infect other cells.

RNA is nucleic acid, and its single-stranded, helical structure is constructed by nucleotides of nitrogenous bases, ribose sugar, and phosphate group; the bases are adenine, guanine, cytosine, and uracil, for which, 1’ nitrogen of pyrimidine base and 9’ nitrogen of purines base are bonded to 1’carbon of pentose sugar by glycosidic bond; base pairs of adenine and uracil and of cytosine and guanine are bonded by hydrogen bonds; the ribose is a pentose sugar of carbon numbered from 1’ to 5’ and has a hydroxyl group on the 2’ carbon; the 3’ and 5’ carbons of ribose sugar are bonded to phosphate group by phosphodiester bond; more importantly, the structure is of A-form geometry, which is constructed as of vast and thin major groove and of flat and broad minor groove, the structure can fold on itself to form secondary structure, such as tRNA and rRNA, and the secondary structure that are stabilized by hydrogen bonds, domains of loops, and metal ions, such as Mg 2+, form specific tertiary form.

Double Stranded RNA

Double Stranded RNAs, or dsRNA, are RNA's that have a complementary strand, similar to that of DNA. Many viruses are made from dsRNAs that infect a variety of hosts, ranging from animals, humans, fungi, plants, and bacteria. An RNA virus is a virus that contains only RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. An example of a RNA virus is Hepatitis B, because even though it has a double-stranded DNA genome, the genome is transcribed into RNA during replication. An interesting fact about RNA viruses is that they have very high mutation rates since they lack DNA polymerases which is responsible for finding and editing mistakes. dsRNA's can also be synthetically produced by the process of in vitro and cloning using PCR to amplify the results. dsRNA's are responsible for the RNAi pathway.

Double strand RNA, dsRNA, is important because it helps regulating genes expression in eukaryotes cells. It triggers different gene silencing known as RNAi-Interfering RNA. Interfering RNA is a dsRNA that gets chopped off into a smaller fragments and binds to mRNA to block the gene expression. It also helps to reduce the production of gene’s encoded protein in order to get just right growth and reduce the self defense.

Structure

RNA is usually found in humans as a single stranded linear polymer. The monomeric units (nucleotides) linked together by 3'5' phosphodiester bridges. (A nucleoside is a ribose sugar connected to a base through the 1'C, while a nucleotide is a nucleoside plus a phosphate group connected to the 5'C of the sugar) The secondary structure of RNA is stabilized by Hydrogen bonds, intrastrand pairing of the bases (AU, GC) oftentimes resulting in structures such as hairpin loops. The stability of these loops depend on the number of unpaired bases in the loop, anything more than 10 or less than 5 is not very energetically favorable. There are oftentimes when the structure of RNA is not very stable because of the inability to match up Watson and Crick base pairs in the stem of the hair pin loops. Because it is single stranded, RNA will also fold into more complex structures, there are times when three nucleotides interact together to stabilize the structure. The Mg²⁺ stabilizes the structure when it is more elaborately structured. In these cases, there are often Hydrogen bond donors or acceptors that aren't already in Watson and Crick base pairs can interact and Hydrogen bond in 'irregular' pairing. Because of the extra hydroxyl group attached to the anomeric Carbon (the 2' Carbon), RNA is not as stable as DNA and will not form double helices as easily, although there have been cases of them found in some viruses. The 2' hydroxyl group on RNA also causes it to self hydrolyze. The hydroxyl group will attack the phosphorous which cleaves the phosophodiester bond on the 5' end. This instability also contributes to DNA being the preferred molecule for genetic storage in humans.

The technique of Northern blotting is often used to uncover the DNA sequence of a sample.

Types

There are many different types of RNA, and they carry out different function in the cell.

mRNA

Messenger RNA

Transcribes the DNA and is the template for the synthesis of protein. DNA + RNA polymerase makes mRNA.
tRNA

Transfer RNA

Brings the activated amino acids from other parts of the cell to the site of translation, or the ribosome. tRNA reads the information in th emRNA and translates that to amino acid. In other words, it translates information from the RNA to proteins.
rRNA

Ribosomal RNA

RNA that takes part in translating Messenger RNA into protein, constituent of ribosomes. rRNA is the most common and deals with the activity of the ribosome. rRNA deals with the formation of peptide bonds and is carried by this RNA in the ribosome.
siRNA: Small interfering RNA; Bind to Messenger RNA and help them degrade.
miRNA

Micro RNA

Small non-coding RNA that inhibit translation of their complementary mRNA.
snRNA: small nuclear RNA; Responsible for the sorting of proteins by removal of the introns (splicing) from hnRNA as well as maintaining telomeres
RNAi: Interference RNA; inhibition of gene expression by cutting up mRNA.; Structural insights into RNA interference.

The structures of these different types of RNA will vary depending on what they are supposed to do. The tertiary structure varies by function. Even in the simplest sense, some will be relatively long strands of nucleic acids, such as Messenger RNA up to 1.2 kilobases, while others are relatively short sequences of 21 nucleotides such as miRNA.

References