Poly-A site

Splice site 3 Splice sites Poly(A) site... 

FIGURE 26-19 Two mechanisms for the alternative processing of complex transcripts in eukaryotes, (a) Alternative cleavage and polyadenylation patterns. Two poly(A) sites, A, and A2, are shown. 

FIGURE 26-20 Alternative processing of the calcitonin gene transcript in rats. The primary transcript has two poly(A) sites one predominates in the brain, the other in the thyroid. In the brain, splicing eliminates the calcitonin exon (exon 4) in the thyroid, this exon is re-... 

The processing pathways that lead to the two forms of mRNA are illustrated in Figure 8. To produce mRNA encoding ps, a primary transcript is cleaved and polyadenylated at a proximal poly(A) site located 3 to the exon encoding C 4 and the terminal segment of the secreted chain. To produce mRNA encoding pm, the transcript is cleaved and polyadenylated at a distal poly(A) site 3 to the membrane exons. The primary transcript for pm is spliced from the border between... 

Cp4 and the secreted segment to the 5 border of the first membrane exon the donor splice site lies within a GGU glycine codon that is retained in ps mRNA. Which form of mRNA is produced depends on competition between splicing and polyadenylation at the p.s and pm poly(A) sites (Peterson and Perry, 1986 Tsurushita et al., 1987 Galli et al., 1988 Peterson and Perry, 1989). The balance between the two mRNA products determines the proportion of membrane and secreted IgM. Activation of the B lymphocyte appears to tip the balance in favor of secretion, but the regulatory signals are not known. 

Galli, G., Guise, J., Tucker, P.W., Nevins, J.R. (1988). Poly(A) site choice rather than splice site choice governs the regulated production of IgM heavy-chain RNAs. Proc. Natl. Acad. Sci. USA 85, 2439-2443. 

Peterson, M.L. Perry, R.P. (1989). The regulated production of and ps mRNA is dependent on the relative efficiencies of ps poly(A) site usage and the Cp4-to-Ml splice. Mol. Cell. Biol. 9,726-738. 

NOS promoter TnS NPT1J Coding Soquenco NOS poly A site... 

Another type of regulation of processing involves choice of different sites of polyadenylation. One example is the differential synthesis of the hormone calcitonin in different tissues another is the synthesis of two forms of the heavy chain of immunoglobulins (Chapter 35). In both cases, the differential processing includes distinct patterns of intron excision (i.e., splicing), but they are necessitated by an earlier event in which differential poly(A) sites are selected from the primary transcript. That is, when the poly(A) site nearer the promoter is selected, a splice site used in the larger primary transcript is not present, so a different splice pattern results. Thus, slightly different proteins are synthesized. 

The run time of the algorithm grows approximately linearly with the sequence length. Fgenes is based on the linear discriminant functions developed for identifying splice sites, exons, promoter and poly-A sites [61, 68]. We consider these functions in the following sections to see which sequence features are important in exon prediction. 

Use of alternative poly(A) sites, producing mRNAs that share the same 5 exons but have different 3 exons (Figure... 

A FIGURE 12-2 Overview of mRNA processing in eukaryotes. Shortly after RNA polymerase II Initiates transcription at the first nucleotide of the first exon of a gene, the 5 end of the nascent RNA Is capped with 7-methylguanylate (step ). Transcription by RNA polymerase 11 terminates at any one of multiple termination sites downstream from the poly(A) site, which Is located at the 3 end of the final exon. After the primary transcript Is cleaved at the poly(A) site (step S),... 

In most protein-coding genes, a conserved AAUAAA poly(A) signal lies slightly upstream from a poly(A) site where cleavage and polyadenylatlon occur. A GU- or U-rlch sequence downstream from the poly(A) site contributes to the efficiency of cleavage and polyadenylatlon. 

Because of alternative splicing of primary transcripts and cleavage at different poly(A) sites, different mRNAs may be expressed from the same gene In different cell types or at different developmental stages (see Figure 12-14). 

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