What is RNA?
Ribonucleic acid (RNA) is another molecule present in a cell. RNA is located in the cell nucleus and is composed of a single strand of alternating sugar (ribose) and phosphate groups, along with nitrogen bases (adenine, uracil, cytosine, guanine). Thymine (found in DNA) is not found in RNA; it is replaced by uracil. For RNA, adenine pairs with uracil, while guanine pairs with cytosine.
The main function of RNA is to produce proteins using a process called protein synthesis, which consists of two phases, transcription and translation.
Gene expression is the phenotypic manifestation of genes by the processes of transcription and translation. Gene expression via transcription and translation is a fundamental principle of molecular biology that is often referred to as the central dogma of molecular biology.
Gene expression in humans is complex and highly regulated. Regulation occurs at many points during the transcription and translation processes and involves epigenomic compounds, which are chemical compounds and proteins that can attach to DNA and influence gene expression.
Transcription occurs in the cell’s nucleus. The main purpose of the transcription process is to produce and process messenger RNA (mRNA). RNA is involved in coding, decoding, regulation and expression of genes. RNA is single stranded and contains the nucleotide uracil instead of thymine. RNA also contains ribose sugar molecules. The mRNA contains the information for making a protein and transports the information out of the nucleus and into the cell’s cytoplasm.
Translation occurs in the cell’s cytoplasm. The main purpose of the translation process is protein synthesis. Ribosomes reach the mRNA and read the sequence of the bases. Each sequence of three bases is called a codon, and each codon contains the instructions for one amino acid. Transfer RNA (tRNA) is another type of RNA. The tRNA assembles the protein using the amino acids. The protein continues to be built until a stop codon is encountered. A stop codon is a three-base sequence that does not code an amino acid.
Three different types of RNA molecules are required for transcription and translation, and each type of RNA has a different function. When genes are “turned on,” RNA polymerase attaches to the start of the gene and then moves along DNA, creating a single strand of mRNA. mRNA contains the protein coding instructions and moves from the cell nucleus through the cytoplasm. In the mRNA, each “triplet” (or three nucleotide sequence) forms a codon. Codons on the mRNA are read by the ribosomal RNA (rRNA; a component of the ribosome) and matched up to the transfer RNA (tRNA) molecule. Each codon specifies a particular amino acid (the building blocks of a protein).
When the ribosome attaches to the mRNA, the codons are read. tRNA matches up to each codon delivering the matching amino acid and adding to the growing amino acid chain (protein). One start codon (AUG) and several stop codons (UAA, UAG, UGA) indicate the start and stop of the amino acid chain. The start and stop codons do not code for any of the 20 amino acids.
What is a protein?
Proteins are the result of DNA transcription and translation. Proteins are macromolecules made of one or more polypeptide chains, which are made up of a sequence of 20 different amino acids. Proteins bind to other molecules called ligands. After polypeptide chain(s) are completed, the chain(s) fold over onto themselves to create a 3-dimensional structure. The resulting polypeptide chains direct the function of the protein in the cell.
Proteins facilitate many functions that support human life.
Antibodies bind to foreign particles (eg, viruses, bacteria) to protect the body. White blood cells, specifically B lymphocytes, produce antibodies. Antibodies are typically “Y” shaped.
Enzymes perform or catalyze chemical reactions in cells (eg, muscle contraction). Enzymes assist with bodily functions such as digestion and DNA replication.
Messenger proteins transmit signals to coordinate biological processes that occur between different cells, tissues and organs. Hormones (eg, insulin, oxytocin) are great examples of messenger proteins.
Structural proteins provide structure and support for cells. Actin filaments and microtubules are examples of structural proteins. There are three types of structural proteins: fibrous, globular and membrane. Fibrous proteins form hair, nails and skin.
Transport proteins bind and carry atoms and small molecules. Hemoglobin is a transport protein in red blood cells that is used to carry oxygen from the lungs to other tissues.
Because proteins are critical to supporting human life, it is imperative that they function properly. Dysfunctional proteins can result in uncontrolled tumor growth and spread in patients with cancer.
Gene regulation is the process of turning genes on or off. Gene regulation can occur at any point of the transcription-translation process but most often occurs at the transcription level.
Proteins that can be activated by other cells and signals from the environment are called transcription factors. Transcription factors bind to regulatory regions of the gene and increase or decrease the level of transcription. Other mechanisms of gene regulation include regulating the processing of RNA, the stability of mRNA and the rate of translation.
Turning the correct genes on and off is an essential component to maintaining a cell’s functionality.
An epigenetic change is a modification to DNA that occurs when a chemical compound or protein attaches to a gene and alters gene expression. The actual DNA sequence is not changed, but rather the chemical or protein is attached to the DNA. Epigenetic changes can be passed down through inheritance or can occur through exposure to environmental substances, as a result of lifestyle behaviors or due to increasing age.
One example of epigenetic change is methylation. Methylation occurs when small molecule methyl groups are added to DNA. The addition of these groups to DNA results in the gene being turned off, and thus the protein made from that gene is not produced.
The epigenome changes throughout a person’s life.
Many scientists have contributed to the development of genome-editing technology. Emmanuelle Charpentier, PhD, and Jennifer Douda, PhD, are often considered pioneers in the field. In 2015, they published a paper on using a bacterial system called clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) or CRISPR-Cas9 technology to edit genomes.
The CRISPR technology can make precise changes in human DNA by slicing out the incorrect portion of the gene and replacing it. It is a complicated process, but simply put, “guide” RNA and a bacterial enzyme, called Cas-9, bind to and cut DNA. A repair template with the desired change is inserted where the DNA has been cut. Multiple DNA edits can be made simultaneously.
Editing DNA with CRISPR has many advantages. For example, genome editing could potentially prevent or treat genetic diseases such as cystic fibrosis, hemophilia and sickle cell anemia. Research is also being done on DNA editing in the treatment of more complex diseases, such as cancer. CRISPR technology is quick and fairly easy for trained scientists.
Although there are many benefits of using CRISPR, the technology also has some limitations. Although CRISPR technology is precise, it is not perfect. It sometimes cuts DNA that is similar to the guide RNA, but not exact.
CRISPR has been one of the biggest scientific achievements of the century. However, with progress comes considerations. There are complicating ethical issues to evaluate when considering DNA editing. For example, is it appropriate to edit the genomes of human embryos? Should we cure disease? Do edits we make today have unforeseen impacts to future generations? How does commercialization of gene editing technologies fit in? Should CRISPR technology be available to the scientific masses, or should its use be limited to selected experts? These questions remain up for debate as conversations about CRISPR technology continue. While this debate continues, leaders in genetics and bioethics have proposed a moratorium on germline gene editing.