Messenger Rna (Mrna)

Genes transcribe their encoded sequences as a RNA template that plays the role of precursor for messenger RNA (mRNA), being thus termed pre-mRNA. Messenger RNA is formed through the splicing of exons from pre-mRNA into a sequence of codons, ready for protein translation. Therefore, mRNA is also termed mature mRNA, because it can be transported to the cytoplasm, where protein translation will take place in the ribosomal complex.

Transcription occurs in the nucleus, through the following sequence of the events. The process of gene transcription into mRNA in the nucleus begins with the orginal DNA nitrogenous base sequence represented in the direction of transcription (e.g. from the 5' (five prime) end to the 3' (three prime end) as DNA 5'... AGG TCC TAG TAA...3' to the formation of pre-mRNA (for the exemplar DNA cited) with a sequence of 3'... TCC AGG ATC ATT...5' (exons transcribed to pre-mRNA template) then into a mRNA sequence of 5'... AGG UCC UAG UAA...3' (codons spliced into mature mRNA).

Messenger RNA is first synthesized by genes as nuclear heterogeneous RNA (hnRNA), being so called because hnRNAs varies enormously in their molecular weight as well as in their nucleotide sequences and lengths, which reflects the different proteins they are destined to code for translation. Most hnRNAs of eukaryotic cells are very big, up to 50,000 nucleotides, and display a poly-A tail that confers stability to the molecule. These molecules have a brief life, being processed during transcription into pre-mRNA and then in mRNA through splicing.

The molecular weight of mRNAs also varies in accordance with the protein size they encode for translation and they necessarily are much bigger than the protein itself, because three nucleotides are needed for the translation of each amino acid that will constitute the polypeptide chain during protein synthesis. Therefore, the molecular weight of mRNAs varies from some hundreds to thousands of Daltons. In prokaryotic cells, mRNA molecules can even be longer. Bacteria, for instance, have a long mRNA molecule that can be translated from different regions, thus resulting in more than one different protein, depending upon the site where the translation starts. Prokaryotic mRNA molecules usually have a short existence of about 2-3 minutes, but the fast bacterial mRNA turnover allows for a quick response to environmental changes by these unicellular organisms. In mammals, the average life span of mRNA goes from 10 minutes up to 2 days. Therefore, eukaryotic cell in mammals have different molecules of mRNA that show a wide range of different degradation rates. For instance, mRNA of regulatory proteins, involved either in cell metabolism or in the cell cycle control, generally has a short life of a few minutes, whereas mRNA for globin has a half-life of 10 hours.

The enzyme RNA-polymerase II is the transcriptional element in eukaryotic cells that synthesizes messenger RNA. The general chemical structure of most eukaryotic mRNA molecules contain a 7-methylguanosine group linked through a triphosphate to the 5' extremity, forming a cap. At the other end (i.e., 3' end), there is usually a tail of up to 150 adenylils or poly-A. One exception is the histone mRNA that does not have a poly-A tail. It was also observed the existence of a correlation between the length of the poly-A tail and the half-life of a given mRNA molecule.

The RNA molecules are linear polymers that share a common basic structure comprised of a backbone formed by an alternating polymer of phosphate groups and ribose (a sugar containing five carbon atoms). Organic nitrogenous bases i.e., the purines adenine (A) and guanine (A), and the pyrimidines cytosine (C) and uracil (U) are linked together through phosphodiester bridges. These four nitrogenous bases are also termed heterocyclic bases and each of them combines with one of the riboses of the backbone to form a nucleoside, such as adenosine, guanosine, cytidine, and uridine. The combination of a ribose, a phosphate, and a given nitrogenous base by its turn results in a nucleotide, such as adenylate, guanylate, cytidylate, uridylate. Each phosphodiester bridge links the 3' carbon at the ribose of one nucleotide to the 5' carbon at the ribose of the subsequent nucleotide, and so on. RNA molecules fold on themselves and form structures termed hairpin loops, because they have extensive regions of complementary guanine-cytosine (G-C) or adenine-uracil (A-U) pairs. Nevertheless, they are single polynucleotide chains.

The mRNA molecules contain at the 5' end a leader sequence that is not translated, known as UTR (untranslated region) and an initiation codon (AUG), that precedes the coding region formed by the spliced exons, which are termed codons in the mature mRNA. At the end of the coding region, three termination codons (UAG, UAA, UGA) are present, being followed by a trailer sequence that constitutes another UTR, which is by its turn followed by the poly-A tail. The stability of the mRNA molecule is crucial to the proper translation of the transcript into protein. The poly-A tail is responsible by such stability because it prevents the precocious degradation of mRNA by a 3'to 5' exonuclease (a cytoplasmatic enzyme that digests mRNA starting from the extremity 3' when the molecule leaves the cell nucleus). The mRNA of histones, the nuclear proteins that form the nucleosomes, do not have poly-A tails, thus constituting an exception to this rule. The poly-A tail also protects the other extremity of the mRNA molecule by looping around and touching the 7-methylguanosine cap attached to the 5' extremity. This prevents the decapping of the mRNA molecule by another exonuclease. The removal of the 7-methylguanosine exposes the 5' end of the mRNA to digestion by the 5'to 3' exonuclease exonuclease (a cytoplasmatic enzyme that digests mRNA starting from the 5' end). When the translation of the protein is completed, the enzymatic process of deadenylation (i.e., enzymatic digestion of the poly-A tail) is activated, thus allowing the subsequent mRNA degradation by the two above mentioned exonucleases, each working at one of the ends of the molecule.