Drosophila splicing

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. 

Shen, J., Beall, C. J., and Hirsh, J. (1993). Tissue-specific alternative splicing of the Drosophila dopa decarboxylase gene is affected by heat shock. Mol. Cell. Biol. 13,4549 555. 

Morgan, B., Johnson, W. A., and Hirsh, J. (1986). Regulated splicing produces different forms of dopa decarboxylase in the central nervous system and hypoderm of Drosophila melanogaster. EMBO J. 5 3335-3342. 

The role of PARP-1 as a modulator of chromatin stiucture, as well as its chromatin-dependent effects on transcription, has been well established in the literature (D Amours et al, 1999 Kraus and Lis, 2003 Rouleau et al, 2004 Kim et al, 2005). In this section, we will highlight some of the historical studies, as well as more recent studies, that have characterized the role of PARP-1 and PAR in these processes. Note that, when describing this work, the term PARP in the absence of any additional identifiers refers to PAR-generating proteins of ambiguous identity (e.g., as in early studies, which were conducted without the knowledge that multiple PARP family members exist, or when multiple splice variants of a PARP-1-like protein exist in a single organism, as in Drosophila). 

Alternative splicing could have arisen accidentally, but it is controlled by proteins. Best known is the alternative splicing factor (ASF or SF2).612,637 It was first recognized by its function in Drosophila melano-gaster, where the sex of individuals is determined by alternative splicing of an mRNA.638 In addition to ASF other serine- and arginine-rich SR proteins participate in alternative splice site selection.612... 

Burtis, K. C., and B. X. Baker, Drosophila double sex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56 997-1010, 1989. 

The need for diversity in 5-HT receptor-mediated signaling must have arisen relatively early in evolutionary history, as some invertebrate species have multiple 5-HT receptor subtypes. For example, at least four subclasses of 5-HT receptors are known from the Anopheles mosquito, Aplysia, and Drosophila, and at least seven from the nematode Caenorhabditis elegans. Additional diversity in signaling is provided by alternative splicing (see subsequent chapter). 

Koushika SP, Soller M, White K (2000) The neuron-enriched splicing pattern of Drosophila erect wing is dependent on the presence of ELAV protein. Mol Cell Biol 20 1836-1845 Kremer EJ, Pritchtird M, Lynch M, Yu S, Holman K et al (1991) Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252 1711-1714 LaFetla EM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer s disease. Nat Rev Neurosd 8 499-509... 

This novel function of neurofibromin in Drosophila has not yet been found in mammals and, conversely, attempts to show that neurofibromin regulates Ras in Drosophila have failed. But, since adenylyl cyclase activity in humans is controlled by heterotrimeric G-protein-coupled receptors for hormones, one should check whether neurofibromin affects heterotrimeric G-protein activation in general, and in the nervous system in particular. Since some alternatively spliced variants of mammalian neurofibromin are expressed in neurons, it is also possible that modulation of cyclase activity in neurons is carried out by a particular isoform of neurofibromin. 

Wagner, N., Schmitt, J. and Krohne, G. (2004) Two novel LEM-domain proteins are splice products of the annotated Drosophila melanogaster gene CG9424 (Bocksbeutel). Eur. J. Cell Biol. 82, 605-616. 

Mount SM, Steitz JA. Sequence of Ul RNA from Drosophila melanogaster implications for U1 secondary structure and possible involvement in splicing. Nucleic Acids Res. 1981 9 6351-6368. 

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