Alternative splicing generates two distinct Eip28/29 gene transcripts in Drosophila Kc cells.

Schulz, Robert A.; Cherbas, Lucy; Cherbas, Peter

doi:10.1073/pnas.83.24.9428

Cited by 21 publications

(4 citation statements)

References 19 publications

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“…As a consequence, the alternative 5' splice donor site created at the boundary of exon 1 and exon 2 in this RNA intermediate is only 12 bases away from the 5' splice donor site at the boundary of exon 2 and intron 2. In examples of internal, alternative 5' splice donor sites in primary transcripts, a situation somewhat analogous to the RNA intermediate of the rat AMPDJ transcript, the distance between alternative 5' splice donor sites is rather short (6 to 27 bases) (18,19,24,32,33,37). Thus, one factor that may operate to prevent random utilization of internal 5' splice donor sites generated by exon ligation during constitutive splicing is exon size.…”

Section: Methodsmentioning

confidence: 99%

A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

Mineo¹,

Clarke²,

Sabina³

et al. 1990

Mol. Cell. Biol.

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AMP deaminase (AMPD) is a central enzyme in eucaryotic energy metabolism, and tissue-specific as well as stage-specific isoforms are found in many vertebrates. This study demonstrates the AMPDI gene product in rat is alternatively spliced. The second exon, a 12-base miniexon, was found to be excluded or included in a tissue-specific and stage-specific pattern. This AMP deaminase (AMP aminohydrolase; EC 3.5.4.6) (AMPD) activity has been found in all eucaryotic cells examined thus far, but it is not present in procaryotes, which suggests that this enzyme catalyzes a reaction that is important for energy metabolism in the specialized environment of the eucaryotic cell. Tissue-specific and stage-specific isoforms of AMPD have been reported in many vertebrates (14,22,23). In human and rats, two functional AMPD genes have been identified (16a). AMPDJ is expressed at high levels in skeletal muscle; AMPD2 is expressed in many nonmuscle tissues of the adult animal as well as in embryonic muscle, cardiac muscle, and smooth muscle. Two clinical phenotypes of inherited AMPD deficiency have been described in humans. Homozygous deficiency of AMPD activity restricted to erythrocytes has been estimated to have a frequency of -0.03% in Japanese, Chinese, and Koreans (21). Deficiency of AMPD restricted to skeletal muscle is a common cause of inherited metabolic myopathy in the United States and Europe (30), and the latter phenotype is presumably a consequence of mutations in the AMPDJ gene.Alternative splicing is used in many tissues, including skeletal muscle, to generate protein diversity (2). Prior studies suggest that more than one transcript may be produced from the AMPDJ gene in rat skeletal muscle. RNase mapping experiments performed with an AMPDI probe demonstrated the presence of two transcripts that have identical or closely related 5' and 3' termini, but the internal sequences of these transcripts diverge at one or more points (29). The study described here demonstrates that two mRNAs are produced from the rat AMPDJ gene and that the only difference between these two transcripts is the inclusion or exclusion of exon 2, a 12-base miniexon. The relative abundance of these two AMPD1 transcripts is regulated by tissue-specific and stage-specific signals. This pattern of alternative splicing exhibited by rat AMPDJ has been referred to as cassette splicing. It has been assumed in this type of splicing, the variably retained exon is removed as a part of a larger intron that contains the exon as well as both of the flanking introns (2). The study presented here demonstrates that this is not the only mechanism for cassette splicing. In the case of AMPDI, a novel pathway for alternative splicing has been identified. This pathway requires the formation of an RNA intermediate that generates a functional, alternative 5' splice donor site at the point where exon 1 is ligated to exon 2. The analogous RNA intermediate of the human AMPDI transcript generates a potential 5' splice donor site at the boundary of exon 1 and exon 2 that i...

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Section: Methodsmentioning

confidence: 99%

A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

Mineo¹,

Clarke²,

Sabina³

et al. 1990

Mol. Cell. Biol.

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“…In this case, any difference in the length of trailer sequences becomes irrelevant. But alternative splicing can also affect the size and coding region of exons, as shown by Schulz et al (1986) study of the Drosophila Eip 28/29 gene (see Fogle, 1990). Therefore, alternative splicing also challenges model D, and the conclusion we reach is that none of the structural models discussed above holds.…”

Section: The Classical Molecular Gene Conceptmentioning

confidence: 77%

Between the cross and the sword: the crisis of the gene concept

El-Hani

2007

Genet. Mol. Biol.

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Challenges to the gene concept have shown the difficulty of preserving the classical molecular concept, according to which a gene is a stretch of DNA encoding a functional product (polypeptide or RNA). The main difficulties are related to the overlaying of the Mendelian idea of the gene as a 'unit': the interpretation of genes as structural and/or functional units in the genome is challenged by evidence showing the complexity and diversity of genomic organization. This paper discusses the difficulties faced by the classical molecular concept and addresses alternatives to it. Among the alternatives, it considers distinctions between different gene concepts, such as that between the 'molecular' and the 'evolutionary' gene, or between 'gene-P' (the gene as determinant of phenotypic differences) and 'gene-D' (the gene as developmental resource). It also addresses the process molecular gene concept, according to which genes are understood as the whole molecular process underlying the capacity to express a particular product, rather than as entities in 'bare' DNA; a treatment of genes as sets of domains (exons, introns, promoters, enhancers, etc.) in DNA; and a systemic understanding of genes as combinations of nucleic acid sequences corresponding to a product specified or demarcated by the cellular system. In all these cases, possible contributions to the advancement of our understanding of the architecture and dynamics of the genetic material are emphasized.

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“…The Drosophila Eip 28/29 gene produces two primary polypeptide products that are induced by the hormone ecdysone (Schulz et al, 1986). The gene, composed of four exons, encodes two processed mRNAs that differ in length by 12 internal nucleotides resulting in translated polypeptides that differ by 4 amino acids.…”

Section: Model Dmentioning

confidence: 99%

Are genes units of inheritance?

Fogle

1990

Biol Philos

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Definitions of the term 'gene' typically superimpose molecular genetics onto Mendelism. What emerges are persistent attempts to regard the gene as a 'unit' of structure and/or function, language that creates multiple meanings for the term and fails to acknowledge the diversity of gene architecture. I argue that coherence at the molecular level requires abandonment of the classical unit concept and recognition that a gene is constructed from an assemblage of domains. Hence, a domain set (1) conforms more closely to empirical evidence for genetic organization of DNA regions capable of transcription and (2) has ontological properties lacking in the traditional unit definition.

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Alternative splicing generates two distinct Eip28/29 gene transcripts in Drosophila Kc cells.

Cited by 21 publications

References 19 publications

A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1.

Between the cross and the sword: the crisis of the gene concept

Are genes units of inheritance?

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