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Learning Objective

By the end of this section, you will be able to:

  • Differentiate three types of RNA and their functions
  • Describe gene regulation process.
  • Understand epigenetic modification and explain the process
  • Explain genomic Editing and CRISPR Technology

Three Types of RNA and Their Functions

There are three different types of RNA including messenger RNA, ribosomal RNA, and transfer RNA.

mRNA or Messenger RNA:
mRNA transcribes the genetic code from DNA into a form that can be read and used to make proteins. mRNA carries genetic information from the nucleus to the cytoplasm of a cell.

rRNA or Ribosomal RNA:
rRNA is located in the cytoplasm of a cell, where ribosomes are found. rRNA directs the translation of mRNA into proteins.

rRNA or Ribosomal RNA:
Like rRNA, tRNA is located in the cellular cytoplasm and is involved in protein synthesis. Transfer RNA brings or transfers amino acids to the ribosome that corresponds to each three-nucleotide codon of rRNA. The amino acids then can be joined together and processed to make polypeptides and proteins.

Gene Regulation

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.

Epigenetic Modification

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.

Gene/Genome Editing

Many scientists have contributed to the development of genome-editing technology. 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.

Genome Editing with CRISPR

CRISPR/Cas9 edits genes by precisely cutting DNA and then letting natural DNA repair processes to take over. The system consists of two parts: the Cas9 enzyme and a guide RNA.

Three Main Categories of Genetic Edits Performed with CRISPR/Cas9

DISRUPT
If a single cut is made, a process called non-homologous end joining can result in the addition or deletion of base pairs, disrupting the original DNA sequence and causing gene inactivation.

DELETE
A larger fragment of DNA can be deleted by using two guide RNAs that target separate sites. After cleavage at each site, non-homologous end joining unites the separate ends, deleting the intervening sequence.

CORRECT OR INSERT
Adding a DNA template alongside the CRISPR/Cas9 machinery allows the cell to correct a gene, or even insert a new gene, using a process called homology directed repair.


CRISPR Terminology

  • CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats of genetic information that some bacterial species use as part of an antiviral system. A group of scientists, including our co-founder Dr. Emmanuelle Charpentier, discovered how to use this system as a gene-editing tool.
  • Cas9: a CRISPR-associated (Cas) endonuclease, or enzyme, that acts as “molecular scissors” to cut DNA at a location specified by a guide RNA.
  • Deoxyribonucleic acid (DNA): the molecule that most organisms use to store genetic information, which contains the “instructions for life”.
  • Ribonucleic acid (RNA): a molecule related to DNA that living things use for a number of purposes, including transporting and reading the DNA “instructions”.
  • Guide RNA (gRNA): a type of RNA molecule that binds to Cas9 and specifies, based on the sequence of the gRNA, the location at which Cas9 will cut DNA.

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