Messenger RNAs (mRNAs) are single-stranded molecules in cells that transfer genetic information from the DNA in the nucleus to the cytoplasm, where proteins are synthesized (in the ribosomes). mRNAs are a group of RNAs that can be translated into proteins, while other RNAs cannot. Because nearly every function in the organisms is carried out by one or many proteins, mRNA is just as critical as DNA. The sequence of mRNA can be interpreted using next-generation sequencing (NGS). Transcriptomics using RNA-seq can explore the sequence and function of mRNA.
In prokaryotes (organisms lacking a distinct nucleus), mRNAs contain a transcribed copy of the DNA sequence with a terminal 5′-triphosphate group and a 3′-hydroxyl residue. In eukaryotes (organisms containing a clearly defined nucleus), the structure of mRNA molecules is more elaborate. The 5′-triphosphate residue is further esterified, forming a cap structure. The 3′ ends typically contain a poly(A) tail that consists of multiple adenosine monophosphates and is added enzymatically after transcription. Eukaryotic mRNA molecules, usually composed of introns and exons, are subjected to a process of cleavage and rejoined from an original precursor mRNA. In general, due to the lack of the poly(A) tail and the cap structure, prokaryotic mRNAs are less stable than eukaryotic mRNAs and degraded very rapidly.
The central dogma is the flow of genetic information from DNA, to RNA, and to protein. Because DNA cannot be decoded directly to produce amino acids, mRNAs act as an intermediary between DNA and protein. Each piece of mRNA encodes the information for one protein in eukaryotes (or more than one protein in prokaryotes). During translation, ribosomes use the instructions conveyed by mRNA as a template for recruiting and assembling the amino acids to create the desired peptides/protein. Every three nitrogen-containing bases in the mRNA directing the incorporation of a particular amino acid within the protein or the termination of the translation process. In addition to mRNA, two other major types of RNA also take part in protein synthesis, which are ribosomal RNA (rRNA) and transfer RNA (tRNA). rRNA is the component of ribosomes. tRNA is responsible for carrying specific amino acids to the ribosome.
mRNA and Disease
Abnormal gene expression, caused by DNA mutation, can bring about the transcription of defective instructions, leading to failure, insufficiency or excess to produce a protein, or the production of dysfunctional proteins. Defect in protein may cause serious genetic diseases.
Recently, mRNA-based therapeutics are emerging as a promising class of therapeutic agents. It leverages the critical role of mRNAs in protein synthesis. Some companies have developed technologies to generate mRNA sequences that cells recognize as if they were produced endogenously. Thus, proteins created by the given mRNA sequences will enable the body to prevent or fight a specific disease.
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