RNA Processing:- A Gene Can Give Rise to Multiple Products by Differential RNA Processing
The transcription of introns seems to consume cellular resources and energy without returning any benefit to the organism, but introns may confer an advantage not yet fully appreciated by scientists. Introns may be vestiges of a molecular parasite not unlike transposons . Although the benefits of introns are not yet clear in most cases, cells have evolved to take advantage of the splicing pathways to alter the expression of certain genes. Most eukaryotic mRNA transcripts produce only one mature mRNA and one corresponding polypeptide, but some can be processed in more than one way to produce different mRNAs and thus different polypeptides. The primary transcript contains molecular signals for all the alternative processing pathways, and the pathway favored in a given cell is determined by processing factors, RNA binding proteins that promote one particular path.
Complex transcripts can have either more than one site for cleavage and polyadenylation or alternative splicing patterns, or both. If there are two or more sites for cleavage and polyadenylation, use of the one closest to the 5end will remove more of the primary transcript sequence (Fig. 1a). This mechanism, called poly(A) site choice, generates diversity in the variable domains of immunoglobulin heavy chains. Alternative splicing patterns (Fig. 1b) produce, from a common primary transcript, three different forms of the myosin heavy chain at different stages of fruit fly development. Both mechanisms come into play when a single RNA transcript is processed differently to produce two different hormones: the calcium-regulating hormone calcitonin in rat thyroid and calcitonin-gene-related pep tide (CGRP) in rat brain (Fig. 2).
FIGURE 1 Two mechanisms for the alternative processing of complex transcripts in eukaryotes. (a) Alternative cleavage and polyadenylation patterns. Two poly(A) sites, A1 and A2, are shown.
(b) Alternative splicing patterns. Two different 3 splice sites are shown. In both mechanisms, different mature mRNAs are produced from the same primary transcript.
FIGURE 2 Alternative processing of the calcitonin gene transcript in rats. The primary transcript has two poly(A) sites; one pre dominates in the brain, the other in the thyroid. In the brain, splicing eliminates the calcitonin exon (exon 4); in the thyroid, this exon is retained. The resulting peptides are processed further to yield the final hormone products: calcitonin-gene-related peptide (CGRP) in the brain and calcitonin in the thyroid.
