Polyadenylation

Eukaryotic mRNA capping poly-a tails occur when RNA is created, then mRNA copies one strand, the ends are modified with 5’ and 3’ ends, and then poly adenylation occurs adding a strand of A nucleotides to the end. The purpose of this technique in cellular biology is that it helps the cell to determine whether or not the mRNA is ready to be exported and translated into a protein. The ends also help to determine the type of protein that it will be translated into (Alberts, 2008).

One disease specifically associated with eukaryotic mRNA capping poly-A tails is myotonic dystrophy. Patients suffering from MD experience skeletal muscle myotonia and degeneration, which can be fatal. The most common form of this disease is found in adults and is a autosomal dominant disease which occurs from an abnormal CUG expansion in the 3’ translated region of the DM protein kinase mRNA (Hurt and Silver, 2008). Normally, DM protein kinase is transcribed and then transported for splicing before it is transported out of the nucleus, but in the presence of an expanded CUG repeats, prevents the entry of RNA and the messages accumulate at the foci of the splicing domains (Hurt and Silver, 2008).This disease has been implanted in both fly and mouse models and they exhibit many of the same physiological and cellular characteristics as human patients.

The history of this topic’s research is that polyadenylation was first discovered in 1960s as an enzymatic activity that could polymerase ATP (Edmonds, 1960). The actual known function of this wasn’t known until 1971, when polyadenylated tail sequences were discovered in RNA. At first it was only thought to cap on the 3’ end of mRNA but then later found that it is also important in export and translation (Edmonds, M., 2002).

Different research articles have used this technique of mRNA capping and poly-A tails to identify or create different outcomes for their mRNA sequence. 1. The Importance of polyadenylation in this paper is that by adding yPAP to the cleavage system of mRNA, they were able to achieve a specific poly-a tail addition. They discovered that at least some of the yeast polyadenylation-related proteins work in the plant system (Zhao, 2011). This could potentially become useful in crossing bacterial and plant genes for a future study.

2. The mRNA capping technique is important in this paper because it forms a covalent complex with RNA viruses at the 5’ phosphorylated viral mRNA start sequence and the mRNA is capping is catalyzed by the RNA. The structural identification of mRNA is the 5’ terminal cap structure. This is what distinguishes mRNA from other types of RNA and makes it recognizable for export and translation (Ogino, 2011).

3. The importance of this technique in this paper is that poly(A) tails are found on almost every successfully processed eukaryotic mRNA, and it influences the stability, the translation and the transport of the mRNA. This paper is looking at alternative polyadenylation in higher eukaryotic mRNAs. Type one is only present in 3’ UTR, which produces on one mRNA isoform. Type two, has more than one polyadenylation signal but it is only found at the terminal exon. Type two produces more than on mRNA but there is no effect on the encoded protein, but there may be a change in the number of proteins produced. Type three has signals that are present upstream in the introns or exons and initiates alternative splicing and polyadenylation. These different types of polyadenylation can result in changes in gene expression under different circumstances (Lutz and Moreira, 2012).

References:


 * Alberts, B. (2008). Molecular biology of the cell (5th ed.). New York: Garland Science.


 * Edmonds, Mary; Abrams, Richard (1960). [|"Polynucleotide Biosynthesis: Formation of a Sequence of Adenylate Units from Adenosine Triphosphate by an Enzyme from Thymus Nuclei"]. The Journal of Biological Chemistry 235 (4): 1142–9. [|PMID] [|13819354].
 * Edmonds, M (2002). "A history of poly A sequences: from formation to factors to function". Progress in Nucleic Acid Research and Molecular Biology Volume 71. Progress in Nucleic Acid Research and Molecular Biology 71. pp. 285–389. [|doi]:[|10.1016/S0079-6603(02)71046-5]. [|ISBN] [|978-0-12-540071-8].


 * Lutz C.S., and Moreira A. (2011). Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene expression. Wiley Interdiscip Rev RNA2: 23–31.
 * Ogino, T. and Banerjee, A.K., (2011). An unconventional pathway of mRNA cap formation by vesiculoviruses. Elsevier,162(1-2): 100-109.


 * Zhao, H., Zheng, J., and Li, Q. Q., 2011. A Novel Plant in Vitro Assay System for Pre-mRNA Cleavage during 3’ – End Formation. Plant Physiology 157: 1546-1554. Doi: 0.1104/pp.111.179465