RNA polyadenylation

Bienroth, S., Keller, W. and Wahle, E. Assembly of a processive messenger RNA polyadenylation complex (1993) EMBO J. 12, 585-94... 

Manley J. L. (1995) Messenger RNA polyadenylation A universal modification. Proc. Natl. Acad. Sci. USA 92 1800. 

Vidarabine is an inhibitor of viral DNA synthesis. Cellular enzymes phosphorylate vidarabine to the triphosphate, which inhibits viral DNA polymerase activity in a manner that is competitive with deoxyadenosine triphosphate. Vidarabine triphosphate is incorporated into both cellular and viral DNA, where it may act as a chain terminator. Vidarabine triphosphate also inhibits ribonucleoside reductase, RNA polyadenylation, and 5 -adenosylhomocysteine hydrolase, an enzyme involved in transmethylation reactions. Resistant variants due to mutations in viral DNA polymerase can be selected in vitro. 

Ji G, Zheng J, Shen Y, Wu X, Jiang R, Lin Y, Loke JC, Davis KM, Reese GJ, Li QQ (2007) Predictive modeling of plant messenger RNA polyadenylation sites. BMC Bioinform... 

A classification-based prediction model of messenger RNA polyadenylation sites. J Theor Biol 265(3) 287-296. doi 10.1016/j.jtbi. 

Ji G, Wu X, Li Q, Zheng J (2010) Messenger RNA polyadenylation site recognition in green alga Chlamydomonas Reinhardtii. Lect Notes Comput Sci 6063 17-26. doi 10.1007/ 978-3-642-13278-0 3... 

Messenger RNA polyadenylation is an important aspect of gene expression in eukaryotes. The process itself is physically and temporally coupled with several other steps in gene expression, ranging from the initiation of transcription to the export of the mature mRNA to the cytoplasm. In the cytoplasm, the poly(A) tail constitutes an essential cis-element that enables the translation of the mRNA, in cooperation with the 5 -cap. 

Nuclear oxidative phosphorylation is difficult to quantify. Although oxygen uptake in the nucleus can be measured, no exact P/O ratio is available. This is because only the AMP already present in the nuclear preparation can be converted to ATP any AMP added to the nuclei remains unaltered. An intriguing observation is the effect of DNase on the phosphorylation of AMP. (Allfrey has proposed that DNase blocks ATP synthesis in the nucleus indirectly namely, by inhibition of the nuclei by the histones, which after DNA extraction are no longer associated with DNA by salt linkages [35].) The enzymic extraction of 55% of the DNA in the nucleus leads to the loss of nuclear phosphorylation properties, which can be restored by adding DNA to the system. The effect of DNA is not specific because DNA can be replaced by RNA, polyadenylic acid, heparin, chondroitin sulfate, and polyethylene sulfate. Oxidative phosphorylation in thymus nuclear preparation has been confirmed in two laboratories. Whole body doses of ionizing radiation inhibited oxidative phosphorylation in thymus nuclei. 

Ara-A is phosphorylated in mammalian cells to ara-AMP by adenosine kinase and deoxycytidine kinase. Further phosphorylation to the di- and triphosphates, ara-ADP and ara-ATP, also occurs. In HSV-1 infected cells, ara-A also is converted to ara-ATP. Levels of ara-ATP correlate directly with HSV rephcation. It has recently been suggested that ara-A also may exhibit an antiviral effect against adenovims by inhibiting polyadenylation of viral messenger RNA (mRNA), which may then inhibit the proper transport of the viral mRNA from the cell nucleus. 

Figure 37-13. Mechanisms of alternative processing of mRNA precursors. This form of RNA processing involves the selective inclusion or exclusion of exons, the use of alternative 5 donor or 3 acceptor sites, and the use of different polyadenylation sites.

In addition to affecting the efficiency of promoter utilization, eukaryotic cells employ alternative RNA processing to control gene expression. This can result when alternative promoters, intron-exon splice sites, or polyadenylation sites are used. Occasionally, heterogeneity within a cell results, but more commonly the same primary transcript is processed differendy in different tissues. A few examples of each of these types of regulation are presented below. 

The polyadenylation of c-mos mRNA in maturing oocytes is similar to that of other maternal RNAs that are accumulated during oocyte... 

Figure 20.20 Summary of transcription, RNA processing and polypeptide synthesis. Polymerisation of the DNA template by RNA polymerase produces pre-mRNA (the primary transcript) this is transcription. The pre-mRNA is now processed, which involves capping, polyadenylation, editing and splicing (see text). The resultant mRNA transfers from the nucleus to the cytosol, where amino acids are polymerised to produce a polypeptide using the instructions present in the codons of the mRNA.

Splicing is just one of the fonr processes that can modify the mRNA molecnle prior to transfer into the cytosol. The other three are cap formation, polyadenylation and editing of RNA. These are colectively known as RNA processing... 

Polyadenylation This process is the addition of many AMP molecules to the 3 end of the RNA molecule. Once bound it is known as a poly A tail, since it is comprised of 100 or more such adenylate (AMP) residues. The tail is thought to stabilise the mRNA molecule in the cytosol, probably by preventing hydrolysis by an RNAase. 

Fig. 1.46. Alternative polyadenylation in the expression of calcitonin genes of rat. The primary transcript of the calcitonin gene possesses two polyadenylation sites. One site is nsed in the processing of RNA in the thyroid, another site in the brain, and yet another in nerve tissne. The translation of the two mRNAs creates two pre-hormones, from which two different polypeptide hormones (calcitonin and the calcitonin-related peptide", or CGRP) are created via proteolysis.

Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004 10 1957-1966. 

Skaar, D.A. Greenleaf, A.L. The RNA polymerase II CTD kinase CTDK-I affects pre-mRNA 3 -cleavage/polyadenylation through the processing component Ptilp. Mol. Cell., 10, 1429-1439 (2002)... 

RNA is removed during processing. Pol II extends the primary transcript well beyond the cleavage and polyadenylation site ("extra RNA") before terminating transcription. Termination signals for Pol II have not yet been defined. 

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