All living things require proteins for various functions. Within cells, scientists define ribosomes as the makers of those proteins. Ribosomal DNA (rDNA), in contrast, serves as the precursor genetic code for those proteins, and performs other functions as well.
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Ribosomes serve as protein factories inside the cells of organisms. Ribosomal DNA (rDNA) is the precursor code for those proteins, and serves other important functions in the cell.
What Is a Ribosome?
One can define ribosomes as molecular protein factories. At its most simplistic, a ribosome is a type of organelle found in the cells of all living things. Ribosomes can both float freely in the cytoplasm of a cell, or can reside on the surface of the endoplasmic reticulum (ER); when it does this, the ER is referred to rough ER.
Proteins and nucleic acids comprise ribosomes; most of these come from the nucleolus. Ribosomes are made of two subunits, one larger than the other. In simpler life forms such as bacteria and archaebacteria, the ribosomes and their subunits are smaller than in more advanced life forms.
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In these simpler organisms, the ribosomes are referred to as 70S ribosomes and are made of a 50S subunit and a 30S subunit. The “S” refers to the sedimentation rate for molecules in a centrifuge.
In more complex organisms such as people, plants and fungi, ribosomes are larger, and are referred to as 80S ribosomes. Those ribosomes are comprised of a 60S and a 40S subunit, respectively. Mitochondria posses their own 70S ribosomes, hinting at an ancient possibility that eukaryotes consumed mitochondria as bacteria, yet kept them as useful symbiotes.
Ribosomes can be made of as many as 80 proteins, and much of their mass comes from ribosomal RNA (rRNA).
What Do Ribosomes Do?
The chief function of a ribosome is to build proteins. It does this by translating a code given from a cell’s nucleus via mRNA (messenger ribonucleic acid). Using this code, the ribosome will adjoin amino acids brought to it by tRNA (transfer ribonucleic acid). Ultimately this new polypeptide will be released into the cytoplasm and be further modified as a new, functioning protein.
Three Steps of Protein Production
While it is easy to generally define ribosomes as protein factories, it helps to understand the actual steps of protein production. These steps must be done efficiently and correctly to ensure no damage to a new protein occurs.
The first step of protein production is called initiation. Special proteins bring mRNA to the smaller subunit of a ribosome, where it enters via a cleft. Then tRNA is readied and brought through another cleft. All of these molecules attach between the larger and smaller subunits of the ribosome, making an active ribosome. The larger subunit primarily works as a catalyst, whereas the smaller subunit works as a decoder.
The second step, elongation, starts when the mRNA is “read.” The tRNA delivers an amino acid, and this process repeats, elongating the chain of amino acids. The amino acids are retrieved from the cytoplasm; they are supplied by food.
Termination represents the end of the protein manufacture. The ribosome reads a stop codon, a sequence of the gene that instructs it to complete the protein build. Proteins called release factor proteins help the ribosome release the complete protein into the cytoplasm. The newly released proteins can fold or be modified in post-translational modification.
Ribosomes can work at high speed to join amino acids together, and can sometimes join 200 of them a minute! Larger proteins can take a few hours to build. The proteins ribosomes make go on to perform essential functions for life, making up muscles and other tissues. The cell of a mammal can contain as many as 10 billion protein molecules and 10 million ribosomes! When ribosomes complete their work, their subunits come apart and can be recycled or broken down.
Researchers are using their knowledge of ribosomes to make new antibiotics and other medicines. For example, new antibiotics exist that perform a targeted attack on the 70S ribosomes inside bacteria. As scientists learn more about ribosomes, more approaches to new medicines will no doubt be uncovered.
What Is Ribosomal DNA?
Ribosomal DNA, or ribosomal deoxyribonucleic acid (rDNA), is the DNA that encodes ribosomal proteins that form ribosomes. This rDNA makes up a relatively small portion of human DNA, but its role is crucial for several processes. Most of the RNA found in eukaryotes comes from ribosomal RNA that was transcribed from rDNA.
This transcription of rDNA is instated during the cell cycle. The rDNA itself comes from the nucleolus, inside the cell’s nucleus.
The rDNA production level in cells varies depending on stress and nutrient levels. When there is starvation, transcription of rDNA drops. When there are abundant resources, rDNA production ramps up.
Ribosomal DNA is responsible for controlling the metabolism of cells, gene expression, response to stress and even aging. There needs to be a stable level of rDNA transcription to avoid cell death or tumor formation.
An interesting feature of rDNA is its large series of repeated genes. There are more rDNA repeats than needed for rRNA. While the reason for this is unclear, researchers think this may have to do with the need for different rates of protein synthesis as different points in development.
These repetitive rDNA sequences can lead to issues with genomic integrity. They are difficult to transcribe, replicate and repair, which in turn leads to overall instability that can lead to diseases. Whenever rDNA transcription occurs at a higher rate, there is an increased risk for breaks in the rDNA and other errors. Regulation of repetitive DNA is important for the health of the organism.
The Significance for rDNA and Disease
Ribosomal DNA (rDNA) issues have been implicated in a number of diseases in humans, including neurodegenerative disorders and cancer. When there is greater instability of rDNA, problems occur. This is due to the repeated sequences found in rDNA, which are susceptible to recombination events that yield mutations.
Some diseases may occur from increased rDNA instability (and poor ribosome and protein synthesis). Researchers have found that cells from sufferers of Cockayne syndrome, Bloom syndrome, Werner syndrome and ataxia-telangiectasia contain increased rDNA instability.
DNA repeat instability is also demonstrated in a number of neurological diseases such as Huntington’s disease, ALS (amyotrophic lateral sclerosis) and frontotemporal dementia. Scientists think that rDNA-related neurodegeneration arises from high rDNA transcription that yields rDNA damage and poor rRNA transcripts. Problems with ribosome production could also play a role.
A number of solid tumor cancers happen to exhibit rearrangements of rDNA, including several repeat sequences. The rDNA copy numbers affect how ribosomes form, and therefore how their proteins develop. Ramped up protein production by ribosomes provides a clue to the connection between ribosomal DNA repeat sequences and tumor development.
The hope is that novel cancer therapies can be made that exploit the vulnerability of tumors due to repetitive rDNA.
Ribosomal DNA and Aging
Scientists recently uncovered evidence that rDNA also plays a role in aging. Researchers found that as animals age, their rDNA undergoes an epigenetic change called methylation. Methyl groups do not change the DNA sequence, but they alter how genes are expressed.
Another potential clue in aging is the reduction of rDNA repeats. More research is needed to elucidate the role of rDNA and aging.
As scientists learn more about rDNA and how it can affect ribosomes and protein development, there remains great promise for new medicines to treat not only aging, but also deleterious conditions such as cancer and neurological disorders.