Exons alternate splicing

B cell chronic lymphocytic leukemia and mantle cell lymphoma are often associated with deletions within the chromosomal region 13ql4.3. These deletions affect the largest npcRNA gene identified so far. BCMS spans around 560 kb and is composed of at least 50 exons. Alternative splicing is tissue specific, but none of the mature variants have a significant proteincoding potential [15]. 

The insulin-binding domain of the INSR is located within a cystein-rich region of the a-subunits. Alternative splicing of exon 11 generates two isoforms of the a-subunit which differ in their C-terminus and in their tissue distribution (type A leukocytes type B liver type A and B skeletal muscle and fat). The isoforms differ in their affinity to insulin (A > B), but then-relevance for normal and impaired insulin action is not entirely clear [1,2]. 

Fig. 2 cDNA structure of human tropoelastin. The alternating hydrophobic and hydrophilic domains are generally encoded by different exons, shown in white and black, respectively. The arrows indicate the six exons that are subject to alternative splicing in a cassette-like fashion. Reproduced from [8] with permission from John Wiley and Sons, copyright 1998... 

In Drosophila the two tissue-specific mRNAs are generated by alternative splicing of a single primary transcript (Fig. 9). In vertebrates the two tissue specific AADC transcripts are generated from two alternative promoters (Fig. 11) (Albert et al., 1992 Ichinose et al., 1992 Thai et al., 1993). In neural tissue transcription initiates from exon Nl, whereas in non-neural tissue transcription initiates from exon LI. This produces two distinct primary transcripts that are then spliced from the first exon (LI or Nl) to exon 2 to generate two tissue-specific mRNAs. Translation initiates within exon 2, such that the same AADC protein product is synthesized from both AADC mRNAs. 

Although there is a different pattern of exons spliced in the two AADC mRNAs, this apparent alternative splicing is a consequence of differences in transcription. In the non-neural mRNAthat initiates at exon LI,... 

Ichinose, H., Sumi-Ichinose, C., Ohye, T., Hagino, Y., Fujita, K., and Nagatsu, T. (1992). Tissue-specific alternative splicing of the 1st exon generates 2 types of messenger-RNAs in human aromatic L-amino acid decarboxylase. Biochemistry 31 11546— 11550. 

Rohlfs EM, Puget N, Graham ML et al. An Alu-mediated 7.1 kb deletion of BRCA1 exons 8 and 9 in breast and ovarian cancer families that results in alternative splicing of exon 10. Genes Chromosomes Cancer 2000 28[3] 300—307. 

Mayer P, Schulzeck S, Kraus J, Zimprich A, Hollt V. Promoter region and alternative spliced exons of the rat mu opioid receptor gene. J Neurochem 1996 66 2272-2278. 

Transcript discovery Find transcripts (genes) in genomic sequence In these experiments, arrays are made from genomic DNA sequences, rather than from complementary DNAs (cDNAs). Such studies can be used to confirm computational gene predictions and characterize alternative splicing and die boundaries of exons (DNA sequences destined to become part of die mature messenger RNA [mRNA]). 

FIGURE 14-5 Isoforms of the rat H3 receptor. The genomic structure of the receptor (top) shows four exons (boxes, E1-E4) and three introns (bp sizes are in parentheses). Peptide sequences that correspond to translated TM regions are labeled with roman numerals (I—VII). An alternatively spliced region (orange box) is depicted between the stop sequences. Six isoforms of the receptor (labels are on the left) result from alternative splicing. (Modified with permission from reference [2].)... 

FcyRIIB generates three transcripts from alternative splicing of exons encoding either the cytoplasmic region (transcripts bl, b2) or the signal sequence (b3). 

Qi, M., Byers, P. H. (1998). Constitutive skipping of alternatively spliced exon 10 in the ATP7A gene abolishes Golgi localization of the the Menkes protein and produces the occipital horn syndrome. Hum. Mol. Genet. 7, 465-469. 

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