Protein Synthesis

The Earth has a plethora of organisms that live and reproduce all throughout its surface. Depending on what kind of organism, they go through some processes that others life-forms do not need to do. However, the molecules DNA and RNA, which are found in all living creatures, work together in a certain process that is crucial to existence: the formation of proteins. Although all species differ from each other in various ways, the processes by which proteins are synthesized are the same in all.

Protein synthesis is a very complex process. In order to understand the process, there some basics that are essential for cells to create the proper proteins. DNA is a very long and double-stranded molecule that contains coding, through four nitrogen bases (adenine, guanine, thymine, and cytosine), for all the genetic information needed to control what needs to happen, or be expressed, by that particular cell. This includes which proteins are made in the cell. The information for the protein is retrieved by the RNA. RNA is different from DNA in that it is single-stranded and is made from the DNA. RNA is very important to the process of protein synthesis in that it is the intermediate of the genes from the DNA and the amino acids in proteins for which they code for. There are two main stages of protein synthesis in every organism: transcription and translation. Transcription is the formation of RNA, specifically mRNA, by DNA, while translation is the formation of polypeptides, the monomers or building blocks of protein, by mRNA and transfer RNA (tRNA). The four nitrogen bases of DNA when transcribed into RNA are read in groups of three called codons, which code for specific amino acids. There sixty-four possible combinations of three nitrogen bases that can form codons. All the proteins in bodies are formed from only twenty amino acids stuck together on long polypeptide chains that later become functional proteins (Wu 1). How come there are only twenty amino acids when there are sixty-four possible combinations of codons? That is because codons are redundant in that multiple codon combinations can produce the same amino acid (and three of the possible codon combinations are stop codons that do not code for an amino acid), however codons are not ambiguous. A codon cannot code for more than one amino acid. These same codons and amino acids are possible in any organism, which is why protein synthesis is known to be universal.

As stated in the last paragraph, transcription is the synthesis, or forming of, RNA under direction of the DNA. Transcription takes place in the nucleus, where all the DNA in the cell is stored. There are three stages to the transcription process in the synthesis of a protein. The first stage starts out with the polymerase binding with the promoter on the regions to be transcribed from the DNA to the mRNA. The polymerase signals the DNA helix to unwind to form an opening for the start of mRNA transcription (UM 1). The promoter is located at the beginning of the region that needs to be transcribed, and sends out a signal to the polymerase so that structure knows where to start unwinding the double helix of the DNA. The binding of the polymerase to the promoter forms what is called the transcription-initiation complex. The whole strands of DNA are not necessary for every protein, so this system helps to conserve energy within the cell by only having to unwind part of the DNA and not all of it. Also, the promoter’s signals are mediated by transcription factors that tell the whether transcription itself is even necessary in that region of the DNA. This first part of transcription is known as the initiation stage. In the next stage, elongation, the RNA strand moves inside the opening and transcribes the sequence of the nitrogenous bases to itself. The RNA polymerase moves along the DNA strands, slowly unwinding a few bases at a time as the single RNA strand binds to one of the two strands of DNA from the 5’ side to the 3’ side by forming the bases that match with the originals on the DNA (Adenine binds with uracil, thymine with adenine, cytosine with guanine, and guanine with cytosine). As the polymerase moves downstream, the parts of the RNA that are already transcribed peel off , and the places where the DNA was previously unwound begin to rewind, which relieves stress on the molecule’s physical structure. Finally, at the termination stage, the RNA transcribes on itself the sequence AAUAAA, which sends off a stop signal that causes the RNA to be released from the DNA strand, which forms the messenger RNA (mRNA) strand. In prokaryotes, single-celled organisms such as bacteria, the mRNA strand goes straight to translation. In eukaryotes, multi-celled organisms, the mRNA will go through another process in between transcription and translation known as RNA modification.

In eukaryotes, the mRNA, which in this instance is more like pre-mRNA, goes through a mini-process call modification, where the pre-mRNA will be altered in certain ways so that it is ready for translation. The first step in modification will alter the ends of the strand. During RNA modification, a modified guanine nucleotide, called a 5’ cap, is added to the 5’ end, and a chain of 50-250 adenine nucleotides, called a poly-A tail, is added to the 3’ end (Campbell 334). These structures are added in order to protect the mRNA strand from degrading as it travels through the cytoplasm to the ribosome, the organelle where transcription takes place. Not only that, but they are also used to easily attach to the ribosome in order to start translation. “By drawing the mRNA’s 5’-end cap through the ribosome entry site and towards the exit, special enzymes such as eIF3 ensure the mRNA is properly positioned for its genetic code to be translated” (Researchers 1). The mRNA has to be in the proper position in the ribosome so the tRNA can bind to the correct codon and produce the right amino acid. The other part of modification is RNA splicing, which is where the sections of the pre-mRNA strand that are not needed in translation are removed. In RNA splicing, small nuclear ribonucleoproteins (snRNPs) form into spliceosomes. Theses spliceosomes then bind to the ends of the regions that aren’t needed for translation and cut these regions off, which causes the remaining strands to bind together. These regions of noncoding segments are located in between the regions of segments that will be coded, and are known as introns. The regions that are left are known as exons. So, if introns are not going to be coded for any part of a protein, why are those sequences transcribed during RNA synthesis? Introns are actually useful sometimes in making new and possibly beneficial proteins through exon shuffling. Exon shuffling is the rearranging of the exons when introns are spliced away. For different proteins, different parts of the pre-mRNA are removed and kept, which results in many variations from one section transcribed DNA sequences. At the end of RNA splicing, these exons bind together and form a modified mRNA molecule that is ready to make some proteins.

In translation, three kinds of RNA molecules are made. There is the modified mRNA that has codons, groups of three bases that code for a certain amino acid in a polypeptide chain. There is also the tRNA that has anticodons, the inverses of codons that bind to them to form the amino acid. Lastly you have the ribosomal RNA. “A ribosome has an mRNA binding site and 3 tRNA binding sites, known as the A, P, and E sites” (Campbell 339). The mRNA enters the binding site, as mentioned in the last paragraph by inserting the 5’ cap through the small subunit of the ribosomal RNA, where the mRNA binding site is located. As the cap goes through, it disintegrates, as it is no longer needed. When the start codon, AUG, approaches the A site, an anticodon binds to this site on the bigger subunit and the bases UAC on the anticodon will bind to the start codon. The amino acid methionine forms and begins the new chain of polypeptides. The A site holds the tRNA to the amino acid. The P site holds the tRNA as the new amino acid connects to the growing chain of the polypeptide. Lastly, the E site is where the tRNA is ejected from the ribosome. The mRNA continues to move through the ribosome. “Each tRNA molecule is bound to one of the amino acids found in cells. A string of amino acids breaks away as protein, its properties determined by the sequence of acids” (Kolata 2). When the synthesis of the polypeptide chain is complete, a stop codon on the mRNA will approach the A site. When a stop codon reaches the A site, a release factor causes the addition of a water molecule instead of an amino acid. This hydrolyses the bond between the polypeptide chain, the tRNA, and the ribosome (Campbell 341). The water molecule added to the chain breaks the bonds, the tRNA floats away, and the ribosomal RNA subunit break away from each other. This last step is known as the termination of protein synthesis.

Of course, there can sometimes be mistakes in protein synthesis. Mutations in DNA can occur that affect the making of certain proteins. Substitution mutations are when nitrogen bases change into different bases. Point mutations change a single base, while base-pair substitution change the base pair. Some lead into a formation of a stop codon, causing the polypeptide chain to be released prematurely, so they are missing some necessary amino acids in order for the protein to function properly. Other substitutions cause changes from one amino acid to another, making mutant proteins. However some may do nothing, because that new codon may still produce the same amino acid as before, since there are multiple codons that can code for the same amino acid, as stated before. “Getting rid of an amino acid may not affect a protein in quite the same way as substituting another one does” (Building 2). The deletion of one amino acid usually does not affect a protein too much in that it does not shift the reading frame. The reading frame is the way the codons are grouped so the correct amino acids are formed in the polypeptide chain. But not all deletion or insertions are of whole codons. They can also be deletions or insertions of 1 or 2 bases, which causes a shift in the reading frames, which results in the wrong amino acids in a protein, and can have very lethal outcomes. However, these mutations are very rare due to the proofreading molecules that appear in DNA replication that make sure that all the nitrogen bases are correct and fix any changes in the sequence of bases, and they catch most of those mistakes. All in all, most mutations can dangerously affect organisms in that they would have malfunctioning proteins that cause harmful effects.

Mutations are not the only things that can cause protein synthesis to go wrong. In certain cells, they may start to lose proper regulation. “The essential role of RNA as an intermediate between cells’ DNA (genotype) and protein (phenotype) is illustrated by the fact that loss of normal gene regulation has shown to be a cause of diseases such as Alzheimer’s, cancer, and arthritis” (Baer 1-2). This loss of regulation affects the gene expression, which refers to the process by which protein synthesis is directed by the DNA through transcription and translation. Sometimes the regulation of gene expression can be affected by things like the promoter not not signaling the polymerase to bind to it like it should, and does not start the process of protein synthesis during initiation of transcription. That could result in a depletion of certain proteins, which then causes less of an important gene to be expressed. Even though many of these molecular defects can affect the process of protein synthesis, environmental factors can also affect protein synthesis. Conditions, such as high-fat diets, that inhibit the state of homeostasis in the endoplasmic reticulum can cause a decrease in protein synthesis (Research 1). The endoplasmic reticulum is where many ribosomes, the sites of protein synthesis, are located. Too much fat, that is hydrophobic, would cause an effect on translation in that the water molecule from the stop codon would not hydrolyze as well as usual.

Overall, protein synthesis is an essential process that occurs in the same way in all organisms, no matter how different, since it regulates the impact on genes and how each organism is supposed to function in order to survive in their world.

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