mRNA, also known as messenger RNA, is a single stranded RNA molecule that is complementary to the DNA. It carries the genetic information present in the DNA and is translated to form proteins. The genetic codes (triplet) present on mRNA are translated to amino acids, which are the functional product of a gene (proteins).

In eukaryotes, mRNA is synthesised in the nucleus and then transported to the cytoplasm, where it undergoes processing and translation or protein synthesis.

Types of RNA

RNA (Ribonucleic Acid) is a type of nucleic acid found in cells that plays a role in a variety of biological processes, such as protein synthesis, gene expression, regulation, and cell signaling. Additionally, some viruses have RNA as their genetic material.

RNA synthesis (also known as transcription) is the process of creating RNA from DNA using the enzyme RNA polymerase, which is a DNA-dependent enzyme.

The three main types of RNA present in a cell are:

• Messenger RNA (mRNA)
• Ribosomal RNA (rRNA)
• Transfer RNA (tRNA)

All three types of RNA are involved in the synthesis of proteins.

1. mRNA - It is a single-stranded RNA molecule that acts as a messenger between the DNA and the protein synthesis process. It contains the genetic information encoded in the DNA that is used to create proteins.

2. tRNA - It is a small RNA molecule of around 80 nucleotides in length. Its primary purpose is to decode the mRNA template and transfer the corresponding amino acid to the ribosome for protein synthesis.

3. rRNA - It plays a structural and catalytic role in protein synthesis, forming the catalytic part of ribosomes. Eukaryotic ribosomes contain four different types of rRNA: 18S, 5.8S, 28S, and 5S rRNA.

Other types of non-coding regulatory RNAs include: microRNA (miRNA), small nuclear RNA (snRNA), Small interfering RNA (siRNA), etc.

Now let us delve into the details of mRNA.

mRNA Structure

Messenger RNA (mRNA) is a type of RNA that is single-stranded and acts as a template for protein synthesis, which is carried out by ribosomes.

Jacob and Monad coined the term “messenger RNA”, which is a long polymeric molecule composed of nucleotides.

mRNA is a long, single-stranded molecule consisting of nucleotides attached by phosphodiester bonds. It contains four nitrogenous bases: adenine, guanine, cytosine, and uracil. The RNA is complementary to one of the DNA strands, except for uracil instead of thymine in DNA.

The mature mRNA consists of the following regions:

• 5′ cap
• 5′ UTR
• coding region
• 3′ UTR
• poly(A) tail

Coding Region - It is composed of codons, a sequence of three nucleotides. Each codon codes for a specific amino acid, and mRNA codons are translated into amino acids by ribosomes to form a polypeptide chain. The coding region starts with the start codon, AUG, and ends with any of the stop codons, UAG, UAA, or UGA. Additionally, some parts of the coding sequence may have a regulatory role.

Untranslated Regions (UTRs) - UTRs are located at the 5’ and 3’ regions before and after the coding region, respectively. Before the start codon and after the stop codon, UTRs are present. They are involved in gene expression, RNA stability, translation efficiency, and mRNA localization.

5’ Cap - A cap of methyl guanosine triphosphate is present at the 5’-end.

Poly(A) Tail: Polyadenylate tail is present at the 3’-end.

Most eukaryotic mRNAs code for a single protein, known as monocistronic. On the other hand, in prokaryotes, most mRNAs code for more than one protein, called polycistronic. These proteins are usually related in function and are regulated by a single regulatory region containing a promoter and operator region. In humans, the mitochondrial genome is also polycistronic.

Synthesis of mRNA: Transcription and Processing

RNA is synthesised from DNA through the process of transcription.

In prokaryotes, a single DNA-dependent RNA polymerase catalyzes the transcription of all types of RNA. Here, mRNA does not require any processing, so transcription and translation can be coupled, since both processes occur in the cytosol.

In eukaryotes, RNA polymerase II transcribes pre-mRNA or primary transcript, which is known as hnRNA or heterogeneous nuclear RNA. After processing, the mature mRNA is transported to the cytosol and translation occurs.

Transcription

The process of synthesizing RNA from DNA is called Transcription. The DNA-dependent RNA polymerase synthesizes RNA by using DNA as a template, in the 5’ to 3’ direction.

The template strand has 3’ to 5’ polarity, while the coding strand has 5’ to 3’ polarity. The RNA transcribed has the same sequence of nucleotides as the coding strand.

A transcription unit in DNA consists of three main regions and all the references are made with respect to the coding strand.

Promoter - located at the 5’ end of the structural gene.

Structural Gene: Present between Promoter and Terminator.

Terminator - located at the 3’ end of the structural gene.

The Transcription Process is Carried Out in Three Steps:

3.

1. Initiation - RNA polymerase binds to the promoter region and forms a transcription bubble by unwinding the DNA double helix, thus starting transcription.

2. Elongation – RNA polymerase continues to use complementary nucleoside triphosphates as substrates and the elongation process proceeds with the unwinding of the DNA double helix. RNA polymerase transcribes RNA in a 5’ to 3’ direction.

3. Termination - Upon arriving at the termination region, transcription ceases and mRNA separates from RNA polymerase.

Processing

The newly formed mRNA or primary transcript is called hnRNA and needs to undergo processing to transform into mature mRNA. The hnRNA undergoes post-transcriptional processing to produce mature mRNA. The functional mRNA is transported out of the nucleus. The translation or protein synthesis takes place in the cytoplasm.

The hnRNA contains both exons and introns, which are coding and non-coding regions respectively. It undergoes splicing, capping and tailing.

Splicing - In this process, introns are removed from the primary transcript and exons are joined together.

Capping - In this process, a cap of an unusual nucleotide, i.e. methyl guanosine triphosphate is added to the 5′-end of hnRNA.

Tailing - In the tailing process, 200-300 adenylate residues are added to the 3’ end. The poly(A) tail helps to protect RNA from degradation by exonucleases and is also involved in the termination of transcription, transport of mRNA and translation.

The fully functional mRNA produced after processing of hnRNA is transported to the cytoplasm through the nuclear pore complex and translated into a polypeptide chain.

Also Check Out: RNA Splicing – Process and Importance

Functions and Applications

The main function of mRNA is to provide a template for the synthesis of protein. This translation is facilitated by ribosomes, which can be present either freely in the cytoplasm or attached to the Rough Endoplasmic Reticulum (RER).

The genetic information present in the RNA is translated into amino acids present in the polypeptide chain. The sequence of nucleotides or codons in the mRNA specifies the sequence of amino acids in a polypeptide chain. Each triplet codon, which is a sequence of three nucleotides is specific for one amino acid it codes for. An amino acid can be coded by more than one codon. Codons do not overlap.

mRNA is a powerful tool used in the synthesis of proteins, which can be modified to cure diseases and be used as a vaccine. Recently, mRNA vaccines have been developed and approved for restricted usage, such as the Pfizer-BioNTech and Moderna vaccines, to protect against COVID-19 infection.