The nucleolus location lies within every cell’s nucleus. Nucleoli are present during protein production in the nucleus, but they disassemble during mitosis. Scientists have discovered that the nucleolus plays an intriguing role for the cell cycle, and potentially for the longevity of humans.
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The nucleolus is a sub-structure of every cell's nucleus, and is primarily responsible for protein production. In interphase, the nucleolus can become disrupted, and therefore it serves as a check for whether mitosis can proceed or not.
What Is the Nucleolus?
One of the sub-structures of a cell’s nucleus, the nucleolus was first discovered in the 18th century. In the 1960s, scientists uncovered the primary function of the nucleolus as a ribosome producer.
The nucleolus location lies within the nucleus of the cell. Under a microscope, it looks like a dark spot housed by the nucleus. The nucleolus is a structure that does not possess a membrane. The nucleolus can be large or small depending upon a cell’s needs. It is, however, the largest object inside the nucleus.
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Various materials comprise the nucleolus. These include granular material made of ribosomal subunits, fibrillar portions mostly made of ribosomal RNA (rRNA), proteins to make up fibrils and some DNA as well.
Typically a eukaryotic cell houses one nucleolus, but there are exceptions. The number of nucleoli is species-specific. In humans, there can be as many as 10 nucleoli after cell division. They eventually morph into a larger, solo nucleolus, however.
The nucleolus location is important due to its multiple functions for the nucleus. It is associated with chromosomes, forming at chromosome sites called _nucleolus organizer region_s or NORs. The nucleolus can change its shape or disassemble entirely during different phases of the cell cycle.
What Are the Functions of the Nucleolus?
The nucleoli are present for ribosome assembly. The nucleolus serves as a sort of ribosome factory, wherein transcription occurs constantly when it is in its fully assembled state.
The nucleolus assembles around bits of repeated ribosomal DNA (rDNA) at the chromosomal nucleolus organizer regions (NORs). Then RNA polymerase I transcribes the repeats and makes pre-rRNAs. Those pre-rRNAs advance, and the resulting subunits assembled by ribosomal proteins eventually become ribosomes. These proteins, in turn, are used for numerous body functions and parts, from signaling, controlling reactions, making hair and so on.
Nucleolar structure is tied to RNA levels, since pre-rRNAs make the proteins that serve as a scaffold for the nucleolus. When rRNA transcription stops, this leads to nucleolar disruption. Nucleolar disruption can lead to cell cycle disruptions, spontaneous cell death (apoptosis) and cell differentiation.
The nucleolus also serves as a quality check for cells, and in many ways it can be considered the “brain” of the nucleus.
Nucleolar proteins are important to the steps of the cell cycle, DNA replication and repair.
The Nuclear Envelope Breaks Down in Mitosis
When cells divide, their nuclei must break down. It eventually reassembles when the process is complete. The nuclear envelope breaks down early in mitosis, dumping a signification portion of its contents in the cytoplasm.
At the beginning of mitosis, the nucleolus disassembles. This is due to the suppression of rRNA transcription by cyclin-dependent kinase 1 (Cdk1). Cdk1 does this by phosphorylating the rRNA transcription components. Nucleolar proteins then move to the cytoplasm.
The step in mitosis at which the nuclear envelope breaks down is the end of prophase. The remnants of the nuclear envelope essentially exist as vesicles at this point. This process does not occur in some yeast, however. It is prevalent in higher organisms.
In addition to the breakdown of the nuclear envelope and disassembly of the nucleolus, the chromosomes condense. The chromosomes become dense in readiness for interphase so they will not become damaged when being arranged into new daughter cells. DNA is tightly wound in the chromosomes at that point, and transcription halts as a result.
Once mitosis is complete, chromosomes loosen up again, and nuclear envelopes reassemble around the separated daughter chromosomes forming two new nuclei. Once the chromosomes decondense, dephosphorylation of rRNA transcription factors occurs. RNA transcription then starts anew, and the nucleolus can begin its work.
To avoid any damage to DNA being passed on to daughter cells, several checkpoints exist in the cell cycle. Researchers think that DNA damage may be at least partially caused by the depletion of rRNA transcription that causes disruption of the nucleolus.
Of course, one of the primary goals of these checkpoints is also to safeguard that daughter cells are copies of parent cells, and possess the correct number of chromosomes.
The Nucleolus During Interphase
Daughter cells enter interphase, which is made of several biochemical steps prior to cell division.
In the gap phase or G1 phase, the cell makes proteins for DNA replication. After this, S phase marks the time of chromosome replication. This yields two sister chromatids, doubling the amount of DNA in a cell.
The G2 phase comes after the S phase. Protein production is ramped up in G2, and of particular note, microtubules are made for mitosis.
Another phase, G0, occurs for cells that are not being replicated. They can be dormant or aging, and some can go on to re-enter the G1 phase to divide.
Following cell division, Cdk1 is no longer needed, and the transcription of RNA can begin again. Nucleoli are present during this point.
During interphase, the nucleolus becomes disrupted. Researchers think this nucleolar disruption results as a response to stress on the cell, due to the suppression of rRNA transcription via DNA damage, hypoxia or lack of nutrients.
Scientists are still teasing out the various roles of the nucleolus during interphase. The nucleolus houses post-translational modification enzymes during interphase.
It is becoming more clear that the structure of the nucleolus is related to the regulation of when cells enter mitosis. Nucleolar disruption leads to delayed mitosis.
The Importance of the Nucleolus and Longevity
Recent discoveries seem to have revealed a connection between the nucleolus and aging. Fragmentation of the nucleolus seems to be the key to understanding this process, as well as damage to ribosomal RNA.
Metabolic processes also seem to play a role with the nucleolus. Since the nucleolus is adaptable to nutrient availability and responds to growth signals, when it has less access to these resources, it decreases in size and makes fewer ribosomes. Cells then tend to live longer as a result, hence the connection to longevity.
When the nucleolus has access to more nutrition, it will make more ribosomes, and it will in turn grow larger. There seems to be a tipping point at which this can become a problem. Larger nucleoli tend to be found in individuals with chronic diseases and cancer.
Researchers are continually learning the significance of the nucleolus and how it works. Studying the processes by which the nucleolus works in cell cycles and ribosomal construction can aid researchers in finding novel treatments to prevent chronic diseases and perhaps increase the lifespan of humans.