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Every cell in our body contains a copy of our genome, the genetic manual for synthesizing proteins whose countless functions form the basis of life. Almost every biological event and process in our body depends on proteins, and various diseases are often the result of the failure of one or more proteins to function properly. However, between DNA and protein, there is a third class of biomolecules: messenger RNA, that is, mRNA. These molecules effectively translate information stored in our genome’s DNA into temporary templates that cells use to produce specific proteins.
What is mRNA?
Before we talk about mRNA, we must first mention DNA. DNA contains all our genes written in a four-letter code – A, C, G and T. DNA is found in the cells of every living thing. It is protected in a part of the cell called the nucleus. Genes are the details of the DNA schema for all of the physical characteristics that make us unique. However, information from genes must travel from the DNA in the nucleus to the main part of the cell – the cytoplasm – where proteins are composed. Cells use proteins to carry out many of the processes necessary for the body to function. This is where messenger RNA, or mRNA for short, comes in.
DNA code fragments are transcribed into abbreviated messages that are instructions for making proteins. These messages – mRNA – are transported to the main body of the cell. After the mRNA arrives, the cell can make specific proteins based on these instructions.
The structure of RNA is similar to DNA but has several important differences. RNA is a single strand of code letters (nucleotides) while DNA is double stranded. The RNA code contains U instead of T – uracil instead of thymine. Both RNA and DNA structures have a backbone made of sugar and phosphate molecules, but the sugar in RNA is ribose and DNA is deoxyribose. DNA sugar contains one less oxygen atom, and this difference is reflected in their names: DNA is the nickname for deoxyribonucleic acid, RNA is ribonucleic acid.
Identical copies of DNA are found in every cell in the body, from the lung cell to the muscle cell to the neuron. RNA is produced as needed in response to the dynamic cellular environment and immediate needs of the organism. The job of mRNAs is to help “activate the cell machinery” to build proteins according to the DNA’s coding that is appropriate for that time and place.
The process of converting DNA into mRNA into protein is fundamental to cell function. Without mRNA, our genetic code would be nothing more than a string of chemicals, and the proteins it encodes would never have been created. In short, our body could not exist.
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Action of mRNA
As an intermediary messenger, mRNA is an important security mechanism in the cell. It prevents invaders from taking control to produce foreign proteins, because any RNA outside the cell is immediately directed for destruction by enzymes called ribonuclease, or for short, RN-ases. When these enzymes recognize the structure and the U in the RNA code, they erase the message, protecting the cell from false instructions.
With mRNA, the cell also gets a way to control the rate of protein production – turn plans on or off as needed. No cell wants to produce every single protein described throughout the genome at the same time.
The mRNA instructions are in sync with self-destruction. The structural features of the mRNA – the U in the code, its single-stranded shape, the ribose sugar and its specific sequence – ensure a short half-life of the mRNA. These characteristics come together to make a message ‘read’ possible, translated into proteins, and then quickly destroyed – within minutes for some proteins that need to be tightly controlled, or within hours for others. When the instructions disappear, protein production stops until the protein factories receive a new message.
See also: Wounds heal badly because RNA gets in the way
Types of mRNA
Pre-mRNA (hnRNA)
Precursor mRNA (pre-mRNA) is the primary transcript of eukaryotic mRNA as it comes out of the template DNA. The pre-mRNA is part of a group of RNAs called heterogeneous nuclear RNA (hnRNA). hnRNA refers to all transcribed single-stranded RNAs (DNA-> RNA) found in the nucleus of the cell, and pre-mRNA makes up a large proportion of these ribonucleic acids.
The pre-mRNA contains sequences that must be spliced before being translated into protein. These sequences can be removed either by the catalytic activity of the RNA itself or by the action of a multi-protein structure called the spliceosome. After this processing step, the pre-mRNA is considered the mature mRNA transcript.
Monocistronic mRNA
A monocistronic mRNA molecule contains exon sequences encoding a single protein. Most eukaryotic mRNAs are monocistronic.
Bicistronic mRNA
A bicistronic mRNA molecule contains exon coding sequences for two proteins.
Polycistronic mRNA
The polycistronic mRNA molecule contains exon coding sequences for many proteins. Most mRNAs of bacteria and bacteriophages (viruses that live in bacterial hosts) are polycistronic.
Also read: MicroRNA: a molecule that can inhibit the replication of human coronaviruses
Prokaryotic versus eukaryotic mRNA
Polycistronic prokaryotic mRNAs contain multiple initiation and termination sites for protein synthesis. Eukaryotes have only one translation initiation site, and eukaryotic mRNAs are predominantly monocistronic. Prokaryotes lack organelles and a well-defined nuclear envelope, and therefore mRNA translation can be coupled to mRNA transcription in the cytoplasm. In eukaryotes, mRNA is transcribed on chromosomes in the nucleus and after processing it is transported through the nuclear pores to the cytoplasm.
In contrast to prokaryotes, translation in eukaryotes does not take place until after transcription is complete. Prokaryotic mRNA is continuously degraded by ribonuclease enzymes that cut RNA. For example, the mRNA half-life in E. coli is about two minutes. Bacterial mRNAs are short-lived, allowing flexibility to adapt to rapidly changing environmental conditions.
Eukaryotic mRNAs are more metabolically stable. For example, precursors of mammalian red blood cells (reticulocytes) that have lost their nucleus synthesize hemoglobin over several days by translating mRNAs that were transcribed while the nucleus was still present. Finally, prokaryote mRNAs undergo minimal processing. In eukaryotes, the pre-mRNA must be processed prior to translation by removing introns, adding a 5 ‘cap, and a 3’ polyadenylated tail before mature mRNA is formed and ready for translation.
MRNA translation
mRNA can be translated on free ribosomes in the cytoplasm by means of transport or transfer RNA molecules (tRNAs) and many proteins called initiation, elongation and termination factors. Proteins that are synthesized on free ribosomes in the cytoplasm are often used by the cell in the cytoplasm itself or directed for use inside intracellular organelles.
Alternatively, proteins that need to be secreted start to be translated in the cytoplasm, but as soon as the first few residues are translated, specific proteins carry the entire translation machinery to the endoplasmic reticulum (RE) membrane. A few of the starting amino acids are embedded in the ER membrane and the rest of the protein is released into the inner space of the ER. The short sequence is removed from proteins that need to be secreted from the cell, while those destined for the inner membranes retain this short length, providing an anchor in the membrane.
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Examples of mRNA processing disorders
Over 200 diseases are associated with defects in the processing of pre-mRNA into mRNA. Mutations in DNA or splicing mechanisms have a great influence on the accuracy of pre-mRNA splicing. For example, an abnormal DNA sequence can eliminate, weaken, or activate hidden splicing sites in pre-mRNA. Likewise, if the splicing mechanisms do not function properly, the spliceosome may incorrectly cleave the pre-mRNA, regardless of sequence.
These mutations result in the processing of pre-mMRA into mRNA that will encode malfunctioning proteins. The abnormal mRNAs themselves are also sometimes a target for the so-called NMD (Nonsense-Mediated Decay), as well as co-transcriptional degradation of the resulting pre-mRNA. Cells from patients with a variety of diseases including progeria, breast cancer, and cystic fibrosis exhibit RNA splicing defects, with cancer and neuropathological diseases being the most common.
Use of mRNA in vaccines
All the features of the mRNA have aroused great interest from vaccine makers. The goal of the vaccine is to make the immune system respond to a harmless version or part of the virus germ, so when we encounter a real ‘problem’ we are ready to fight it. Researchers found a way to introduce and protect mRNA messages coded for the spike protein portion on the surface of the SARS-CoV-2 virus.
The vaccine provides enough mRNA to make enough spike protein for the immune system to make antibodies that protect them if they are later exposed to the virus. The mRNA used in the vaccine is soon destroyed by the cell – just like any other mRNA. mRNA cannot enter the cell nucleus and cannot affect human DNA.
While these are new vaccines, the underlying technology was originally developed many years ago and has been gradually improved. As a result, vaccines have been well tested for safety. The success of these mRNA vaccines against COVID-19 in terms of safety and efficacy predicts a bright future for new vaccine therapies that can be quickly adapted to new emerging threats.
Early clinical trials with mRNA vaccines have already been conducted in influenza, Zika virus, rabies and cytomegaly. Certainly, scientists are already considering and developing treatments for other diseases or disorders that could benefit from an approach similar to that used for COVID-19 vaccines.
See also: The “genetic scissors” technique will help in the fight against COVID-19?
How are mRNA vaccines different from traditional vaccines?
The goal of any vaccine is to train the body to recognize and fight germs by making antibodies and activating immune cells.
Conventional vaccines introduce weakened, dead, or non-infectious parts of the virus or bacteria into the body. In turn, mRNA vaccines instruct the body to make its own viral or bacterial proteins, which the immune system then reacts to.
See also: Is it true that the mRNA vaccine is clean? Here are 21 important questions about it
Advantages of mRNA vaccines over traditional vaccines
There is no risk of infection with the vaccine as mRNA vaccines do not introduce live virus into the body.
Unlike conventional vaccines, mRNA vaccines are not grown in live cells, which speeds up the manufacturing process. MRNA vaccines also bypass virus inactivation or protein isolation, which also speeds up their production.
MRNA vaccines are more effective against microbes that evolve as a result of mutations. This is because RNA vaccines typically elicit an immune response to the part of the virus that does not mutate readily. Traditional vaccines typically target another part of the virus that mutates easily.