Regulation of RNA Processing

Another example of regulation of RNA processing is found in adenovirus, which has only a few promoters but which makes numerous primary transcripts and a large number of mRNAs. A fairly small amount of DNA is used efficiently because proteins are translated in all reading 

The amount of each mRNA is regulated with respect to the time after infection. RNAs 1 and 2 are both formed shortly after the primary transcript is made, although more of mRNA-2 is made. Later in the viral life cycle, mRNA-1 is not made and mRNA-2 is abundant. If cycloheximide, an inhibitor of protein synthesis, is added to the infected cells before the shift in splicing pattern takes place, the shift does not occur. This inhibition implies that a newly synthesized protein is a positive effector of the shift. Cycloheximide has a similar effect on other mRNA species derived from other primary transcripts at late times. 

Adenovirus has a single promoter for all RNA made late in the cycle of infection. The primary transcripts terminate at five major polyadenylation sites. Each termination site influences the splicing pattern by allowing particular in-trons or intron termini to be present or not. The five sets are not used with equal frequency, with the result that most mRNAs encoding various genes are not the same. This is the primary mechanism for determining the relative amounts of the different structural proteins synthesized late in the adenovirus life cycle. 

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. 

Chicken LC1/LC3 gene. Two distinct TATA sequences lead to production of different primary transcripts, which contain the same coding sequences. Two modes of intron excision lead to the formation of distinct mRNA molecules that encode proteins having different amino terminal regions and the same carboxy terminal regions. 

---