The inside of a cell can be a battleground between foreign material and the cell itself. Viruses can release their RNA into human cells during infection, and human cells have mechanisms to protect themselves against these viruses.
However, the protection mechanism is not very specific.cellswill target any single-stranded RNA for degradation, which poses a major problem when humans also synthesize RNA to makeproteins.
To get around this problem, human cells includedpost-transcriptional modificationsRNA synthesized by humans to protect against the hostile environment of the cell. So if you are interested in learning more aboutpost-transcriptional regulation, keep reading!
- First, we will discuss the post-transcriptional control of gene expression.
- Next, we will look at the types of post-transcriptional regulation.
- Next, we will explore post-transcriptional regulation in eukaryotes.
- Finally, we will look at post-transcriptional regulation in prokaryotes.
Post-transcriptional control of gene expression
remember theDogma centralin which instructions in the form of DNA in the cell are converted to RNA before finally becomingproteins(Figure 1).
During transcription, DNA is converted into heterogeneous nuclear RNA (hnRNA). After transcription, a series of enzyme-catalyzed changes calledpost-transcriptional modificationsthey occur to convert hnRNA into functional messenger RNA (mRNA).
ARNhnbecomemRNAafter post-transcriptional modifications
Emeukaryotic cells, both transcriptional and post-transcriptional modifications occur in the nucleus whiletranslationoccurs in the cytoplasm. like virus andbacteriause single-stranded RNA to replicate within the cytoplasm, eukaryotic cells have evolved mechanisms to degrade single-stranded RNA as a protective mechanism.
If hnRNAs without post-transcriptional modifications are released into the cytoplasm, they would be degraded by the cell's own degradation machinery. Post-transcriptional modifications in the nucleus allow the mRNA to avoid self-degradation and survive in the hostile environment of the cytoplasm.
In contrast, prokaryotic cells lack organelles or a nucleus. Therefore, both transcription andtranslationOccur in the cytoplasm. To prevent RNA from being broken down in the cytoplasm, prokaryotes begintranslationbefore transcription is completed.
Thus, prokaryotic cells do not have post-transcriptional modifications, rather prokaryotes have alternative mechanisms to validate mRNA quality and preventviral replica.
Types of Post-Transcriptional Regulation
There are three post-transcriptional modifications that must occur in the hnRNA before it can be released into the cytoplasm as a mature mRNA:
- Addition of a 5' GTP cap.
- Addition of a 3' poly-A tail.
- Removal of introns and retention of exons.
Details of each modification are discussed in the next section.
Post-transcriptional regulation in eukaryotes
Adding a 5' GTP Limit
Remember that RNA and DNA have directionality with a 5' end and a 3' end. At the 5' end of the hnRNA, a7-methylguanylate-triphosphate capalso known as cap 5' GTP. The 5' GTP cap is a modified guanine nucleotide with an additional methyl group at the seventh guanine position.
The addition of the 5' GTP cap is catalyzed by threeenzymesthat are part of the CAP-binding complex. The CAP binding complex will connect the 5' carbon of the GTP cap to the 5' carbon of the first nucleotide to create aBridge triphosphate 5' to 5'.
There are three general functions of the 5' GTP cap:
To assist in RNA processing and RNA export from the nucleus.
Act as a marker to guide the mRNA duringtranslationnot cytoplasm.
To protect the mRNA from degradation.
Added a 3' poly-A tail
Hepolyadenosyl glue (poly-A)it is added to the 3' end of the hnRNA to protect the RNA transcript from rapid degradation in the cytoplasm.
Once any single-stranded RNA strand enters the cytoplasm, it will be rapidly broken down by the cell's breakdown machinery known as3'-exonucleasas. 3' exonucleases rapidly degrade single-stranded RNA from its 3' end as a protective mechanism against viral and bacterial RNA transcripts. Once the mRNA is released into the cytoplasm, it will also be degraded by 3' exonucleases.
However, the poly-A tail acts as a buffer that will be degraded before coding information into the mRNA. The longer the poly-A tail, the longer the mRNA transcript can survive in the cytoplasm. The poly-A tail is also critical for the export of mature mRNA from the nucleus to the cytoplasm.
The addition of the 5' GTP cap and the 3' poly-A tail is illustrated in Figure 2 below.
remember that eukaryotegenesare made up of coding sequences known aséxonsand non-coding sequences known asintrons. Often, introns are spaced between exons, so after DNA is transcribed into RNA, introns must be removed and exons must be reassembled into an mRNA strand (Fig. 3).
The process of removing introns is known asamend. Splicing is done by a complex calledamendedwhich in turn is made up of a non-coding RNA calledsmall nuclear RNA (snRNA)yproteinscalledsmall nuclear ribonucleoprotein(snRNP).
Together they form the splicesome that will recognize intron boundaries and remove them from the RNA to be degraded. The final product is an RNA transcript composed only of exons.
some eukaryotesgenes, however, they are composed of unique combinations of exons. This means that not all exons are transcribed into a mature mRNA.
In Figure 4, different exons are included in the final RNA transcript. On the left, exon 2 but not 3 may be included in mRNA 1, whereas the reverse may be true for mRNA 2. This selective inclusion of exons is known asalternative splicing.Alternative splicing allows different forms of the protein to be produced from the same DNA sequence.
Examples of post-transcriptional regulation
Remember that all cells in the human body have the samegenomeHowever, not all cells look the same or express the same thing.proteins.
The main reason for this difference is that different cells express different genes. Another reason is alternative splicing.cellsit can splice RNA transcripts differently to produce different proteins from the same gene. In fact, 75% of human genes produce multiple forms of the same proteins, increasing the protein's coding potential.genome.
Post-transcriptional modifications are also critical for sex determination in the fruit fly. As in humans, there are certain genes in fruit flies that can be spliced interchangeably to form different versions of the same protein: a specific gene calleddouble sex geneis responsible for determining the sex of a fruit fly. After alternate splicing, a form of thedouble sex proteinwill inhibit genes involved in male fruit fly development.
However, another form of the protein will inhibit the development of the female fruit fly. Importantly, this example illustrates how post-transcriptional modifications can have drastic effects on the organism, even though the gene itself may be identical.
Ultimately, alternative splicing increases the genome's coding potential. Rather than having two independent genetic pathways, the same gene can be expressed differently through alternative splicing to have opposite effects.
double sex genesdetermine the sex of a fruit fly by acting as a molecular switch at the end of the signaling cascade. Thosegenestarget different types ofcellsfor male or female differentiation.
Post-transcriptional regulation in prokaryotes
Unlike eukaryotes, prokaryotes do not have post-transcriptional modifications. The 5' GTP cap, 3' poly-A tail, and introns are unique to eukaryotes. One reason could be due to the spatial separation between the RNA and theproteinsin eukaryotes.
Unlike eukaryotes, prokaryotes have no nucleus, so bothtranscriptionytranslationOccur in the cytoplasm. This means that the RNA does not need to be transported from the nucleus to the cytoplasm. Without this need for transport, translation can occur on the mRNA transcript simultaneously while the mRNA transcript is being constructed.
Therefore, the mRNA would not need to be as carefully protected against degradation astranslationstarts immediately. Without the need for protection and transport, post-transcriptional modifications would not be necessary.
However, prokaryotes have alternative ways of checking mRNA quality. If the ribosome is translating an incomplete or broken mRNA, an 11-amino acid tag is added to the end of the newly synthesized polypeptide. This 11 amino acid tag acts as a signal to proteases within the prokaryotic cell to destroy the complete protein. By destroying the protein, it prevents it from breaking down or becoming incomplete.proteinsto stay in the cell.
Furthermore, without post-transcriptional modifications, mRNAs are rapidly degraded in the prokaryotic cell; therefore,translationmust occur while a new mRNA transcript is being synthesized.
Post-transcriptional regulation: key points
- After transcription, a series of enzyme-catalyzed modifications called post-transcriptional modifications occur to convert the hnRNA into functional messenger RNA (mRNA).
- Emeukaryotic cells, both transcriptional and post-transcriptional modifications occur in the nucleus whiletranslationoccurs in the cytoplasm.
- There are three post-transcriptional modifications: addition of a 5' GTP cap, addition of a 3' poly-A tail, and intron deletion.
- Alternative splicing is the selective inclusion of certain exons so that different forms of a protein can be produced from the same transcript.
- An example of the effects of post-transcriptional modifications is sex determination in the fruit fly.