5.7 Protein Synthesis
Created by: CK-12/Adapted by Christine Miller
The Art of Protein Synthesis
This amazing artwork (Figure 5.7.1) shows a process that takes place in the cells of all living things: the production of proteins. This process is called protein synthesis, and it actually consists of two processes — transcription and translation. In eukaryotic cells, transcription takes place in the nucleus. During transcription, DNA is used as a template to make a molecule of messenger RNA (mRNA). The molecule of mRNA then leaves the nucleus and goes to a ribosome in the cytoplasm, where translation occurs. During translation, the genetic code in mRNA is read and used to make a polypeptide. These two processes are summed up by the central dogma of molecular biology: DNA → RNA → Protein.
Transcription
Transcription is the first part of the central dogma of molecular biology: DNA → RNA. It is the transfer of genetic instructions in DNA to mRNA. During transcription, a strand of mRNA is made to complement a strand of DNA. You can see how this happens in Figure 5.7.2.
Transcription begins when the enzyme RNA polymerase binds to a region of a gene called the promoter sequence. This signals the DNA to unwind so the enzyme can “read” the bases of DNA. The two strands of DNA are named based on whether they will be used as a template for RNA or not. The strand that is used as a template is called the template strand, or can also be called the antisense strand. The sequence of bases on the opposite strand of DNA is called the non-coding or sense strand. Once the DNA has opened, and RNA polymerase has attached, the RNA polymerase moves along the DNA, adding RNA nucleotides to the growing mRNA strand. The template strand of DNA is used as to create mRNA through complementary base pairing. Once the mRNA strand is complete, and it detaches from DNA. The result is a strand of mRNA that is nearly identical to the coding strand DNA – the only difference being that DNA uses the base thymine, and the mRNA uses uracil in the place of thymine
Processing mRNA
In eukaryotes, the new mRNA is not yet ready for translation. At this stage, it is called pre-mRNA, and it must go through more processing before it leaves the nucleus as mature mRNA. The processing may include splicing, editing, and polyadenylation. These processes modify the mRNA in various ways. Such modifications allow a single gene to be used to make more than one protein.
- Splicing removes introns from mRNA, as shown in Figure 5.7.3. Introns are regions that do not code for the protein. The remaining mRNA consists only of regions called exons that do code for the protein. The ribonucleoproteins in the diagram are small proteins in the nucleus that contain RNA and are needed for the splicing process.
- Editing changes some of the nucleotides in mRNA. For example, a human protein called APOB, which helps transport lipids in the blood, has two different forms because of editing. One form is smaller than the other because editing adds an earlier stop signal in mRNA.
- 5′ Capping adds a methylated cap to the “head” of the mRNA. This cap protects the mRNA from breaking down, and helps the ribosomes know where to bind to the mRNA
- Polyadenylation adds a “tail” to the mRNA. The tail consists of a string of As (adenine bases). It signals the end of mRNA. It is also involved in exporting mRNA from the nucleus, and it protects mRNA from enzymes that might break it down.
Translation
Translation is the second part of the central dogma of molecular biology: RNA → Protein. It is the process in which the genetic code in mRNA is read to make a protein. Translation is illustrated in Figure 5.7.4. After mRNA leaves the nucleus, it moves to a ribosome, which consists of rRNA and proteins. The ribosome reads the sequence of codons in mRNA, and molecules of tRNA bring amino acids to the ribosome in the correct sequence.
Translation occurs in three stages: Initiation, Elongation and Termination.
Initiation:
After transcription in the nucleus, the mRNA exits through a nuclear pore and enters the cytoplasm. At the region on the mRNA containing the methylated cap and the start codon, the small and large subunits of the ribosome bind to the mRNA. These are then joined by a tRNA which contains the anticodons matching the start codon on the mRNA. This group of molecues (mRNA, ribosome, tRNA) is called an initiation complex.
Elongation:
tRNA keep bringing amino acids to the growing polypeptide according to complementary base pairing between the codons on the mRNA and the anticodons on the tRNA. As a tRNA moves into the ribosome, its amino acid is transferred to the growing polypeptide. Once this transfer is complete, the tRNA leaves the ribosome, the ribosome moves one codon length down the mRNA, and a new tRNA enters with its corresponding amino acid. This process repeats and the polypeptide grows.
Termination:
At the end of the mRNA coding is a stop codon which will end the elongation stage. The stop codon doesn’t call for a tRNA, but instead for a type of protein called a release factor, which will cause the entire complex (mRNA, ribosome, tRNA, and polypeptide) to break apart, releasing all of the components.
Watch this video “Protein Synthesis (Updated) with the Amoeba Sisters” to see this process in action:
Protein Synthesis (Updated), Amoeba Sisters, 2018.
What Happens Next?
After a polypeptide chain is synthesized, it may undergo additional processes. For example, it may assume a folded shape due to interactions between its amino acids. It may also bind with other polypeptides or with different types of molecules, such as lipids or carbohydrates. Many proteins travel to the Golgi apparatus within the cytoplasm to be modified for the specific job they will do.7 Summary
5.7 Summary
- Protein synthesis is the process in which cells make proteins. It occurs in two stages: transcription and translation.
- Transcription is the transfer of genetic instructions in DNA to mRNA in the nucleus. It includes three steps: initiation, elongation, and termination. After the mRNA is processed, it carries the instructions to a ribosome in the cytoplasm.
- Translation occurs at the ribosome, which consists of rRNA and proteins. In translation, the instructions in mRNA are read, and tRNA brings the correct sequence of amino acids to the ribosome. Then, rRNA helps bonds form between the amino acids, producing a polypeptide chain.
- After a polypeptide chain is synthesized, it may undergo additional processing to form the finished protein.
5.7 Review Questions
- Relate protein synthesis and its two major phases to the central dogma of molecular biology.
- Explain how mRNA is processed before it leaves the nucleus.
- What additional processes might a polypeptide chain undergo after it is synthesized?
- Where does transcription take place in eukaryotes?
- Where does translation take place?
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5.7 Explore More
Protein Synthesis, Teacher’s Pet, 2014.
Attributions
Figure 5.7.1
How proteins are made by Nicolle Rager, National Science Foundation on Wikimedia Commons is released into the public domain (https://en.wikipedia.org/wiki/Public_domain).
Figure 5.7.2
Transcription by National Human Genome Research Institute, (reworked and vectorized by Sulai) on Wikimedia Commons is released into the public domain (https://en.wikipedia.org/wiki/Public_domain).
Figure 5.7.3
Pre mRNA processing by Christine Miller is used under a CC BY-NC-SA 4.0 (https://creativecommons.org/licenses/by-nc-sa/4.0/) license.
Figure 5.7.4
Translation by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.
References
Amoeba Sisters. (2018, January 18) Protein synthesis (Updated). YouTube. https://www.youtube.com/watch?v=oefAI2x2CQM&feature=youtu.be
Parker, N., Schneegurt, M., Thi Tu, A-H., Lister, P., Forster, B.M. (2016, November 1). Microbiology [online]. Figure 11.15 Translation in bacteria begins with the formation of the initiation complex. In Microbiology (Section 11-4). OpenStax. https://openstax.org/books/microbiology/pages/11-4-protein-synthesis-translation
Teacher’s Pet. (2014, December 7). Protein synthesis. YouTube. https://www.youtube.com/watch?v=2zAGAmTkZNY&feature=youtu.be
The movement of ions or molecules across a cell membrane into a region of higher concentration, assisted by enzymes and requiring energy.
Created by: CK-12/Adapted by Christine Miller
Case Study: Cancer in the Family
People tend to carry similar traits to their biological parents, as illustrated by the family tree. Beyond just appearance, you can also inherit traits from your parents that you can’t see.
Rebecca becomes very aware of this fact when she visits her new doctor for a physical exam. Her doctor asks several questions about her family medical history, including whether Rebecca has or had relatives with cancer. Rebecca tells her that her grandmother, aunt, and uncle — who have all passed away — had cancer. They all had breast cancer, including her uncle, and her aunt also had ovarian cancer. Her doctor asks how old they were when they were diagnosed with cancer. Rebecca is not sure exactly, but she knows that her grandmother was fairly young at the time, probably in her forties.
Rebecca’s doctor explains that while the vast majority of cancers are not due to inherited factors, a cluster of cancers within a family may indicate that there are mutations in certain genes that increase the risk of getting certain types of cancer, particularly breast and ovarian cancer. Some signs that cancers may be due to these genetic factors are present in Rebecca’s family, such as cancer with an early age of onset (e.g., breast cancer before age 50), breast cancer in men, and breast cancer and ovarian cancer within the same person or family.
Based on her family medical history, Rebecca’s doctor recommends that she see a genetic counselor, because these professionals can help determine whether the high incidence of cancers in her family could be due to inherited mutations in their genes. If so, they can test Rebecca to find out whether she has the particular variations of these genes that would increase her risk of getting cancer.
When Rebecca sees the genetic counselor, he asks how her grandmother, aunt, and uncle with cancer are related to her. She says that these relatives are all on her mother’s side — they are her mother’s mother and siblings. The genetic counselor records this information in the form of a specific type of family tree, called a pedigree, indicating which relatives had which type of cancer, and how they are related to each other and to Rebecca.
He also asks her ethnicity. Rebecca says that her family on both sides are Ashkenazi Jews (Jews whose ancestors came from central and eastern Europe). “But what does that have to do with anything?” she asks. The counselor tells Rebecca that mutations in two tumor-suppressor genes called BRCA1 and BRCA2, located on chromosome 17 and 13, respectively, are particularly prevalent in people of Ashkenazi Jewish descent and greatly increase the risk of getting cancer. About one in 40 Ashkenazi Jewish people have one of these mutations, compared to about one in 800 in the general population. Her ethnicity, along with the types of cancer, age of onset, and the specific relationships between her family members who had cancer, indicate to the counselor that she is a good candidate for genetic testing for the presence of these mutations.
Rebecca says that her 72-year-old mother never had cancer, nor had many other relatives on that side of the family. How could the cancers be genetic? The genetic counselor explains that the mutations in the BRCA1 and BRCA2 genes, while dominant, are not inherited by everyone in a family. Also, even people with mutations in these genes do not necessarily get cancer — the mutations simply increase their risk of getting cancer. For instance, 55 to 65 per cent of women with a harmful mutation in the BRCA1 gene will get breast cancer before age 70, compared to 12 per cent of women in the general population who will get breast cancer sometime over the course of their lives.
Rebecca is not sure she wants to know whether she has a higher risk of cancer. The genetic counselor understands her apprehension, but explains that if she knows that she has harmful mutations in either of these genes, her doctor will screen her for cancer more often and at earlier ages. Therefore, any cancers she may develop are likely to be caught earlier when they are often much more treatable. Rebecca decides to go through with the testing, which involves taking a blood sample, and nervously waits for her results.
Chapter Overview: Genetics
At the end of this chapter, you will find out Rebecca’s test results. By then, you will have learned how traits are inherited from parents to offspring through genes, and how mutations in genes such as BRCA1 and BRCA2 can be passed down and cause disease. Specifically, you will learn about:
- The structure of DNA.
- How DNA replication occurs.
- How DNA was found to be the inherited genetic material.
- How genes and their different alleles are located on chromosomes.
- The 23 pairs of human chromosomes, which include autosomal and sex chromosomes.
- How genes code for proteins using codons made of the sequence of nitrogen bases within RNA and DNA.
- The central dogma of molecular biology, which describes how DNA is transcribed into RNA, and then translated into proteins.
- The structure, functions, and possible evolutionary history of RNA.
- How proteins are synthesized through the transcription of RNA from DNA and the translation of protein from RNA, including how RNA and proteins can be modified, and the roles of the different types of RNA.
- What mutations are, what causes them, different specific types of mutations, and the importance of mutations in evolution and to human health.
- How the expression of genes into proteins is regulated and why problems in this process can cause diseases, such as cancer.
- How Gregor Mendel discovered the laws of inheritance for certain types of traits.
- The science of heredity, known as genetics, and the relationship between genes and traits.
- How gametes, such as eggs and sperm, are produced through meiosis.
- How sexual reproduction works on the cellular level and how it increases genetic variation.
- Simple Mendelian and more complex non-Mendelian inheritance of some human traits.
- Human genetic disorders, such as Down syndrome, hemophilia A, and disorders involving sex chromosomes.
- How biotechnology — which is the use of technology to alter the genetic makeup of organisms — is used in medicine and agriculture, how it works, and some of the ethical issues it may raise.
- The human genome, how it was sequenced, and how it is contributing to discoveries in science and medicine.
As you read this chapter, keep Rebecca’s situation in mind and think about the following questions:
- BCRA1 and BCRA2 are also called Breast cancer type 1 and 2 susceptibility proteins. What do the BRCA1 and BRCA2 genes normally do? How can they cause cancer?
- Are BRCA1 and BRCA2 linked genes? Are they on autosomal or sex chromosomes?
- After learning more about pedigrees, draw the pedigree for cancer in Rebecca’s family. Use the pedigree to help you think about why it is possible that her mother does not have one of the BRCA gene mutations, even if her grandmother, aunt, and uncle did have it.
- Why do you think certain gene mutations are prevalent in certain ethnic groups?
Attributions
Figure 5.1.1
Family Tree [all individual face images] from Clker.com used and adapted by Christine Miller under a CC0 1.0 public domain dedication license (https://creativecommons.org/publicdomain/zero/1.0/).
Figure 5.1.2
Rebecca by Kyle Broad on Unsplash is used under the Unsplash License (https://unsplash.com/license).
References
Wikipedia contributors. (2020, June 27). Ashkenazi Jews. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Ashkenazi_Jews&oldid=964691647
Wikipedia contributors. (2020, June 22). BRCA1. In Wikipedia. https://en.wikipedia.org/w/index.php?title=BRCA1&oldid=963868423
Wikipedia contributors. (2020, May 25). BRCA2. In Wikipedia. https://en.wikipedia.org/w/index.php?title=BRCA2&oldid=958722957
