by Subhankar Chakraborty

Created on: December 12, 2006   Last Updated: May 02, 2007

Introduction
Every fully processed mRNA in eukaryotic cells has a poly (A) tail at its 3'end. This stretch of polyadenine residues serves several functions including increasing mRNA stability, enhancing its translation and regulating the transport of fully processed mRNA into the cytoplasm(Colgan and Manley, 1997). In vitro, using synthetic mRNAs it was shown that for polyadenylation to occur, a hexameric sequence AAUAAA is absolutely essential. Wigley et al. showed that this hexameric site is absolutely critical and any mutations in it led to loss of polyadenylation. Further, the 2'-OH group of the Uridine residue is also critical and replacing it with 2'-deoxy-Uridine results in loss of adenylation. Apart from the hexameric sequence, it is also essential to have at least eight nucleotides 3' to AAUAAA for optimum polyadenylation. However, there is no specific sequence requirement for the nucleotides between AAUAAA and the 3'end of the mRNA. The same group also showed that reducing the number of nucleotides between the hexamer and the 3'end of the mRNA decreased the number of poly (A) residues added but did not prevent formation of specific protein complexes on the hexamer. Thus, a specific protein complex forms on the AAUAAA hexamer that utilizes the 2'-OH group of the U residue for specific binding, and the poly A polymerase (PAP) enzyme binds to both this complex as well as to the nucleotides 3' of the hexameric sequence. Only when PAP has bound to both the AAUAAA-protein complex and an optimum number of nucleotides (at least 8) will polyadenylation occur at an optimal rate(Wigley et al., 1990).

The fully processed mRNA is subsequently degraded in the cytoplasm. This process involves essentially three sequential steps- deadenylation of the poly (A) tail, removal of the 5' 7-methylguanosine cap and rapid digestion of the mRNA in a 5'3' direction by an exoribonuclease. The 3'poly(A) tail enhances mRNA stability. It achieves this by two main mechanisms- multiple poly (A) binding proteins (e.g. PABP1) that bind to the poly (A) tail thereby protecting the mRNA from nuclease attack, and by regulation of ribosome-mRNA interactions. Work in yeast has shown that the efficiency of decapping (removal of the 5'-methyl guanine cap) is regulated partly by the length of the poly (A) tail and the number of PABP molecules bound to it(Caponigro and Parker, 1995). It is interesting to note that there exists a pathway for deadenylation-independent decapping of the mRNA. Nonsense

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