MRNA splicing

Beyond the classic NK3r, an mRNA splice variant has been also recently identified but no data on its expression and function are available yet, although the extensive deletion of critical regions renders unlikely its functionality (Table 3) [5]. NK3r has been much less... 

Karras J.G., Maier M.A., Lu T, Watt A., Manoharan M. Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine inter-leukin-5 receptor-alpha chain. Biochemistry 2001 40 7853-7859. 

After mRNA splicing, the tropoelastin mRNA is translated at the surface of the rough endoplasmic reticulum (RER) in a variety of cells smooth muscle cells, endothelial and microvascular cells, chondrocytes and fibroblasts. The approximately 70 kDa precursor protein (depending on isoform) is synthesized with an N-terminal 26-amino-acid signal peptide. This nascent polypeptide chain is transported into the lumen of the RER, where the signal peptide is removed cotranslationally [9]. 

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

All eukaryotic cells have four major classes of RNA ri-bosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). The first three are involved in protein synthesis, and snRNA is involved in mRNA splicing. As shown in Table 37-1, these various classes of RNA are different in their diversity, stability, and abundance in cells. 

Spliceosome The macromolecular complex responsible for precursor mRNA splicing. The spliceosome consists of at least five small nuclear RNAs (snRNA Ul, U2, U4, U5, and U6) and many proteins. 

Insulin mRNA splicing rates were estimated from the rate of disappearance of the insulin preRNA signal from beta-cells treated with actinomycin D to block transcription. The two introns in mouse insulin II are not spliced with the same ef-... 

Figure 11. Alternate promoters are used for production of the vertebrate neural and non-neural AADC mRNAs. Non-neural AADC transcription initiates at exon L1, whereas neural transcription initiates at exon N1. The non-neural mRNA splices from exon L1 to 2, since the 5 edge of exon N1 is a site of transcriptional initiation instead of a splice acceptor site. Translation initiates from the same AUG in exon 2 in both mRNAs, producing the same protein product in both tissue types. This scheme holds for both human and rat AADC, although the nomenclature of the exons differs. In rat AADC the exon N1 to 2 splice uses a splice acceptor site 5 bp downstream of the splice acceptor used for the exon L1 to 2 splice (Albert et al., 1992).

Sarmah, B., Chakraborty, N., Chakraborty, S. and Datta, A. (2002) Plant pre-mRNA splicing in fission yeast, Schizosaccharomyces pombe. Biochemical and Biophysical Research Communications, 293 (4), 1209—1216. 

Izaurralde, E., Lewis, J., McGuigan, C., Jankowska, M., Darzynkiewicz, E., and Mattaj, I. W. (1994). A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78, 657-668. 

Alternative mRNA splicing has been reported to generate four 5-HT7 receptor iso forms. However, these iso forms have not been shown to differ in their respective pharmacology, signal transduction or tissue distribution. 

Pellizzoni, L., Kataoka, N., Charroux, B. and Dreyfuss, G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 95 615-624, 1998. 

Zeitlin S, Parent A, Silverstein S, Efstratiadis A (1987) Pre-mRNA splicing and the nuclear matrix. Mol Cell Biol 7(1) 111-120... 

In mouse cerebellum and cerebral cortex by IHC and WB (Zehnder et al, 2001). Gene amplification for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase and nonfunctional mRNA splice variants in human glioblastoma multiforme (Maas et al, 2001 Diesel et al, 2004, 2005). 

Alternatively mRNA splicing in rat adrenal (Zhou et al., 1997b). 

A subsequent study in 2002 of 27 families with a condition known as multiminicore disease (MmD) also linked mutations in SEPNl to disease pathology. Multiple mutations were identified in exons 1, 5, 7, 8, 10, and 11, and the authors also mentioned that this region (RSMD) had been previously linked to MmD. Minicores are lesions by histochemistry of mitochondrial depletion within muscle tissue. The first biochemical study of selenoprotein N aimed to identify the protein localization by immunohistochemistry and found that the primary protein product of several identified mRNAs (splice variants) was a 70 kDa protein present in the endoplasmic reticulum. Two potential ER targeting domains were shown to be present and the peptide expressed from the first exon was shown to be required for localization into the ER. This study also revealed that selenoprotein N was an integral membrane protein that is N-glycosylated. Expression analysis showed pronounced levels in embryonic tissue with a reduction after development and differentiation. 

Makeyev EV, Zhang J, Carrasco MA et al (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol CeU 27 435-448... 

Alternative mRNA splicing detection and analysis of human exonic enhancer sequences using genomic SELEX... 

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