Polyadenylation sites, alternative

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. 

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.

Certain pre-mRNAs contain more than one set of signal sequences for 3 end cleavage and polyadenylation. In some cases, the location of the alternative polyadenylation sites is such that, depending on the site chosen, particular exons may be lost or retained in the subsequent splicing reactions (Fig. 7). Here the effect is to change the coding capacity of the final mRNA so that different proteins are produced depending on the polyadenylation site used. In other... 

The four basic modes of alternative RNA processing include selective splicing, use of an alternate 50 donor site, use of an alternate 30 acceptor site, and use of an alternate polyadenylation site. 

The steady-state level of RNA in the cell is controlled both by RNA synthesis rates and by RNA turnover. What answer best explains how an alternate polyadenylation site might be utilized to control RNA stability ... 

Zhang, L., Ge, L., Parimoo, S., Stenn, K. and Prouty, S.M. Human stearoyl-CoA desaturase alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem J, 340 (Pt 1) (1999a) 255-264. 

Ohara, O., Gahara, Y., Teraoka, H. and Kitamura, T. (1992) A rat brain-derived neurotrophic factor-encoding gene generates multiple transcripts through alternative use of 5 exons and polyadenylation sites. Gene 121 383-386. 

After the gene is transcribed (i.e., posttranscription), regulation can occur during processing of the RNA transcript (hnRNA) into the mature mRNA. The use of alternative splice sites or sites for addition of the poly(A) tail (polyadenylation sites) can result in the production of different mRNAs from a single hnRNA and, consequently, in the production of different proteins from a single gene. 

Collagen al(IX), and a2(IX) Domestic fowl Alternative promoters, alternative polyadenylation sites 2 forms differ by the presence or absence of globular N-terminal domain in cartilage and cornea different macromolecular organisation in two tissues, several transcripts in chondrocytes Nishimura, Muragaki Olsen (1989) Swiderski Solursh (1992a,b)... 

Ozsolak F, Kapranov P, Foissac S, Kim SW, FishUevich E, Monaghan AP, John B, MUos PM (2010) Comprehensive polyadenylation site maps in yeast and hiunan reveal pervasive alternative polyadenylation. Cell 143 1018-1029, PMID 21145465... 

Note that some poly(A) mRNAs, e.g., histone mRNA of yeast, do not carry the AAUAAA sequence in their 3 ends. In these mRNAs, two different classes of polyadenylation sites have been recognized, i.e., a unidirectional site with the sequence UUUUUAU and a bidirectional site with a tripartite sequence UAG UA(U)GU UUU (26). For other mRNAs that have no apparent recognition sequence motifs in their 3 UTR and yet carry poly (A) tails, other additional or alternative structural features may be present such as further internal sequences (5 to the apparent polyadenylation signal) or secondary structures that are required for proper and/or differential polyadenylation. 

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. 

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