What is messenger RNA (mRNA)?
The messenger RNA or mRNA is single-stranded ribonucleic acid. This is a type of nucleic acid that primarily encodes proteins. This small molecule is the transcript of a section of DNA sequence. The mRNA contains information for protein production in a cell.
Certain sections of the deoxyribonucleic acids are expressed into RNA by an enzyme RNA polymerase (different from DNA polymerase that copies DNA). This process is known as transcription. During protein synthesis, it serves as a template for ribosomal protein biosynthesis. Ultimately, this paves the way for polypeptide chain synthesis.
In the case of mRNA-based drugs, cells tend to produce the active protein according to sequence information. In the case of the RNA based vaccines, this protein can act as an antigen.
During transcription, a section of the genetic code is transcribed into a single strand of RNA. Such sections are termed coding regions. This happens under the action of the enzyme RNA polymerase.
The coding DNA strand serves as a matrix for the construction of an RNA strand. The synthesized mRNA encodes a protein in a process of translation.
Prokaryotes have no nucleus and exhibit transcription in the cytoplasm. While in the eukaryotes, the nuclear genome is transcribed in the karyoplasm of the cell nucleus.
In prokaryotes, ribosomes can already attach to the not yet completely synthesized mRNA sequence. And then begin translation. Hence, the synthesis of proteins can start at the same time as transcription, which enables special forms of gene regulation.
In eukaryotes, the primary RNA transcript is at first subjected to various processes in the cell nucleus. Only then it is exported from the nucleus as mRNA into the cytoplasm where the ribosomes are located.
Prokaryotes possess only one type of RNA polymerase for the synthesis of RNA. In contrast, eukaryotes possess different types of RNA polymerases. And primarily the RNA polymerase II catalyzes the synthesis of pre-mRNA.
A major difference between prokaryotic and eukaryotic messenger RNA is that prokaryotic mRNA is usually polycistronic, while eukaryotic messenger RNA is usually monocistronic. This enables prokaryotes to have the information of several genes on only one single mRNA transcript. So synthesis of the encoded proteins and mRNA synthesis occurs simultaneously. One such jointly transcribed region of functionally related genes on the DNA is called an operon.
Eukaryotic pre-messenger RNA (pre-mRNA) processing
In eukaryotic cells, a mature messenger RNA is produced by processing its precursor. The precursor is termed as the hnRNA (heterogeneous nuclear RNA) or pre-mRNA (precursor messenger RNA, pre-mRNA).
These steps take place in the cell nucleus. Then the mRNA enters the cytoplasm through nuclear pores. And eventually, protein biosynthesis takes place via ribosomes.
- Capping: The 5′ end of the RNA molecule gets a 5′ cap structure. This cap consists of a modified form of guanosine, 7-methylguanosine (m7G). The cap protects the RNA from degradation by nucleases and allows the cap-binding complex. This is important for nuclear export, among other things. After transport into the cytosol, the cap aids in the recognition of the mRNA. It does so with the help of a small ribosomal subunit. This helps in initiating translation.
- Polyadenylation: The RNA undergoes polyadenylation at the 3′ end. During this process, a poly-A tail consisting of 30 to 200 adenine nucleotides is attached. This also protects the messenger RNA from enzymatic degradation. In addition, it facilitates both nuclear export and the translation of the mRNA.
- Splicing: Splicing removes certain RNA segments from the original transcript known as introns. Introns usually do not contribute towards the coding information. The remaining segments are joined together as exons. This process takes place in the spliceosome.
The spliceosome is a complex of the hnRNA and the so-called snRNPs (small nuclear ribonucleoproteins). Spliceosome consists of the snRNAs U1, U2, U4, U5, and U6 and about 50 proteins. By alternative splicing, different mRNAs can thus be produced from the same hnRNA. These results when translated can also lead to different proteins.
This is also where various regulatory processes of the cell intervene. Antisense RNA and RNA interference can be used to degrade mRNA. Thus this prevents translation.
Furthermore, nucleotides in a messenger RNA are changed sometimes by the RNA editing process. An example is the mRNA of apolipoprotein B. For example, in some tissues editing in mRNA of apolipoprotein B creates a second stop codon upstream. This codes for a shorter protein with a different function.
Untranslated regions on mRNA are also responsible for regulating transcription as well as translation.
During translation, the coding sequence of nucleic acid bases of mRNA is translated into the amino acid sequence. This results in the formation of one of the polypeptide chains of a protein.
The nucleotide sequence of an open reading frame is read in triplets. Each base triplet is assigned a specific amino acid by means of transfer RNA or tRNA molecules. These are then linked to the preceding one via a peptide bond. This process takes place at the ribosomes in the cytoplasm and represents the actual protein biosynthesis.
In eukaryotic cells, the ribosomes can be free or can attach themselves to the membrane of the endoplasmic reticulum.
On binding to a messenger RNA, the ribosome translates the coding nucleotide sequence of the mRNA. It translates the nucleotide code into the corresponding amino acid sequence of a protein.
The necessary amino acid molecules are carried by tRNA molecules from the cell cytoplasm. A prokaryotic messenger RNA often contains several coding sections (polygenic mRNA). Contrarily, eukaryotic mRNAs are monocistronic and contain only one section with a coding sequence.
A ribosome translates only one messenger RNA at a time. Next, the ribosome then detaches from the mRNA. However, several ribosomes can attach themselves to one mRNA at the same time and synthesize one polypeptide chain each.
Likewise, an mRNA can be read by the ribosome several times in succession. The number of protein molecules formed thus depends on the number of translation processes carried out.
Degradation messenger RNA (mRNA)
The mRNA is enzymatically degraded by a ribonuclease (RNase) and broken down into its nucleotides. These nucleotides can then be used again to build new RNA molecules. This is called degradation.
The messenger RNA degradation marks the end of the life of an mRNA molecule. However, the duration of nuclease activity in the cell can vary. And it is important for the regulation of protein biosynthesis.
In eukaryotes, the degradation process often takes place in specific structures in the cytoplasm. These structures are known as P- bodies. Instead of being degraded for a new translation, mRNA molecules can be temporarily stored in the cytoplasm. Plus, additional ways of regulation are also possible.