Nucleic acids are naturally occurring chemical compounds that often carry cellular information throughout the cell. Nucleic acids help direct protein synthesis which determines the inherited characteristics of every living thing. There are two main classes of nucleic acids: DNA and RNA. DNA (deoxyribonucleic acid) is a double stranded molecule that encodes the information cells need to make proteins, and is present in the nucleus, mitochondria, and chloroplast. RNA (ribonucleic acid), comparatively, is single stranded, relatively short lived, and plays an essential role in making proteins. Nucleic acids across the board, however, have very diverse functions in cell creation, in the storage and processing of genetic information, and energy generation.
Nucleic acids are polynucleotides which are long chainlike molecules composed of a series of nearly identical building blocks, termed nucleotides. Each nucleotide consists of at least three parts; a nitrogen-containing base connected to a sugar backbone attached to a phosphate group.
Fig. 2
Simplified overview of nucleotide base links and overarching three-dimensional structure. Figure made in BioRender.
The nitrogen-containing base can be adenine (A) or guanine (G), cytosine (C), thymine (T), or uracil (U). A/G are termed purines for their double ringed structure, and C/T/U are termed pyrimidines for their single ring. Notably, only U is found in RNA which often replaces T molecules. These bases are connected to a pentose sugar that contains 5 carbons numbered 1' to 5'. In DNA this sugar is deoxyribose and is located on the second carbon of the pentose ring (2'). In RNA this sugar is ribose which lacks a 2'-hydroxyl (-OH) group. Phosphate groups connect successive sugar residues by bridging the 5'-hydroxyl group on one sugar to the 3'-hydroxyl group of the next.
Each DNA and RNA strand has a sense of direction, where the 3' carbon of the deoxyribose of one nucleotide will always organically link to the 5' carbon of the next. Chemically, RNA is similar to DNA however it is much more labile. This is because most RNA molecules are only single stranded, and most do not form stable secondary structures like DNA. Together, these building blocks form the double- or single-helical structure, characteristic to DNA and RNA respectively.
Other Types of Nucleic Acids
Many other types of nucleic acids exist, and each have varying structural dynamics. These nucleic acids are involved in various regulatory processes and can have diverse functions in both normal cellular processes and disease.
Messenger RNA (mRNA), for example, carries genetic information copied from DNA to help with the creation of proteins. mRNAs are long, generally single-stranded, molecules that consist of nucleotides attached by phosphodiester bonds. mRNAs have a 7-methylguanosine cap on their 5' end that protects it from degradation, and a poly(A) tail on their 3' end that aids in stability during transport.
Another type of RNA, transfer RNA (tRNA), helps translate mRNA into proteins. tRNAs exhibit a cloverleaf structure and are specific to each amino acid. This structure consists of a 3' acceptor site, a 5' terminal phosphate, and four “arms” or “loops” that are considered the business ends of the molecule.
Ribosomal RNA (rRNA) is another variant of RNA that exists in a spherical shape. rRNA provides the structural framework for ribosomes which, essential to protein synthesis. Ribosomes contain a large and small ribosomal subunit with an exit (E), peptidyl (P), and acceptor (A) site.
Alternatively, non-coding RNA (ncRNAs) are transcripts that do not encode proteins and cumulatively make up the biggest class of RNAs. ncRNAs are most easily divided into small (<200 nucleotides) and long ncRNAs (>200 nucleotides), that vary in structure and function within the cell.
Fig. 3
Examples of some common nucleic acid types, including mRNA, tRNA, rRNA, & ncRNA. Figure made in BioRender.
Artificial Nucleic Acids
Today there exist many types of artificial nucleic acid analogues, also termed xenonucleic acids (XNAs), which are distinguished from naturally occurring nucleic acids due to alterations in their backbones and/or nucleobases. XNAs have great potential in biomedicine for use as potential therapeutic agents and/or fluorescent probes for medical research. XNAs mimic naturally occurring nucleic acids but have several advantages including facile chemical synthesis and resistance to nuclease-mediated cleavage. For example, peptide nucleic acid (PNA) is a non-charged oligonucleotide analogue that contains an N-aminoethyl glycine-based polyamide structure instead of a sugar backbone. In contrast to natural DNA, PNA binds in antiparallel and parallel orientations to complementary nucleic acids.
Polyamide
Is a synthetic polymer made by the linkage of an amino group of one molecule, and a carboxylic acid group of another molecule
Has recurring amide linkages
Its monomers are diamines and dicarboxylic acids
Examples are nylon, Kevlar (synthetic polyamides) and wool and silk (natural polyamides)
Polyimide
Is a very strong polymer made from imide monomers
Has recurring imide linkages
Its monomers are either dianhydride and diisocyanate or dianhydride and diamine
Examples are Kapton, Apical, and Kaptrex
Locked nucleic acids (LNA) are another form of synthetic oligonucleotides. LNAs have one or more nucleotides in which an extra methylene bridge can fix the ribose backbone into two separate conformations. LNA is particularly attractive for in vivo applications. In the literature, LNA has shown to have increased affinity over other RNA, can exhibit improved mismatch discrimination, has low toxicity, and has increased metabolic stability.
Currently, dozens of other XNAs exist with various conformations. Some other common XNAs include threose nucleic acid (TNA, with a simplified four-carbon threose backbone), glycol nucleic acid (GNA, based on a glycol monomer), and hexitol nucleic acid (HNA, that has a 1',5'-anhydrohexitol sugar).