Processing of mRNA

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.

Finally, this section has focused almost entirely on axonal transport, but dendritic transport also occurs [25]. Since dendrites usually include postsynaptic regions while most axons terminate in presynaptic elements, the dendritic and axonal transport each receive a number of unique proteins. An added level of complexity for intraneuronal transport phenomena is the intriguing observation that mRNA is routed into dendrites where it is implicated in local protein synthesis at postsynaptic sites, but ribosomal components and mRNA are largely excluded from axonal domains [26]. Regulation of protein synthesis in dendritic compartments is an important mechanism is synaptic plasticity [27,28]. The importance of dendritic mRNA transport and local protein synthesis is underscored by the demonstration that the mutation associated with Fragile X syndrome affects a protein important for transport and localization of mRNA in dendrites [27, 29], Similar processes of mRNA transport have been described in glial cells [30]. 

Human ERa has 565 amino acids, greater therefore than the dominant isoform of ER/J, which has 530 amino acids (Kuiper et al. 1996), the isoforms are products of the same gene and are generated by alternate processing of mRNA. Nevertheless, the structure in the domains of both types of ER reflect the general pattern described, except that ER/3 lacks the carboxyterminal F region (Kumar et al. 1987 Nilsson et al. 2001). Both ERa and ERj0, as well... 

To assist in the modification and processing of mRNAs, eukaryotic cells contain in their nuclei small nuclear RNAs (snRNAs), which are complexed with specific proteins to form small nuclear ribonucleoprotein particles (snRNPs). These RNAs have been named U1, U2, U3,.. . , U13 and range in size from 100 to 220 bases. One, U3, is... 

Genes can be altered posttranscriptionally by the processes of mRNA editing and alternative mRNA splicing. 

The pattern of exons and introns (exon-intron-exon-intron-exon) in the a and /3 families of genes is quite old and apparently developed before the separation of these genes some 500 million years ago. The role of introns is unknown, although their base sequences vary. Because the introns are not transcribed, the protein sequences are unchanged. The introns appear to correspond to structural domains within the folded globulin subunits and are requisite for the posttranscriptional processing of mRNA. 

Further details of the nature and regulation of transcription in prokaryotes and eukaryotes and the post-transcriptional processing of mRNA transcripts are given in Chapter 9. 

Another factor that regulates HDL cholesterol levels is the plasma level of cholesteryl ester transfer protein (CETP). CETP, a hydrophobic glycoprotein (M.W. 741,000), facilitates the transfer of cholesteryl esters in HDL and triacylglycerols in LDL and VLDL (see above). In CETP deficiency due to a point mutation (G A) in a splice donor site that prevents normal processing of mRNA, the plasma HDL cholesterol levels of affected individuals are markedly high, with decreased LDL cholesterol. In the affected families, there was no evidence of premature atherosclerosis and, in fact, there was a trend toward longevity. These observations support the role of CETP and the antiatherogenic property of HDL. However, not all factors that elevate HDL levels may be... 

The events in posttranscriptional processing of mRNA are controlled by the phosphorylation state of the carboxy-terminal domain (CTD), part of RNA polymerase II. 

See also Eukaryotic Transcription (from Chapter 28), Processing of mRNA (from Chapter 28), Introns (from Chapter 28)... 

See also Posttranscriptional Processing of rRNA and tRNA, Processing of mRNA... 

Refractory mutations are difficult to detect due to the nature of the molecular defects. If the genomic region is deleted from the mutant allele, the PCR product from genomic DNA will lead to a false conclusion that this gene region is wild-type. Other mutations affect the expression or processing of mRNA from the affected allele, through mutations of promoter... 

Wachter, A. et ak (2007) Riboswitch control of gene expression in plants by splicing and alternative 3 end processing of mRNAs. Plant Cell 19,3437-3450... 

---