Entry - *602718 - TRANSFORMER 2 ALPHA HOMOLOG; TRA2A - OMIM
 
* 602718

TRANSFORMER 2 ALPHA HOMOLOG; TRA2A


Alternative titles; symbols

TRANSFORMER 2, DROSOPHILA, HOMOLOG OF, ALPHA


HGNC Approved Gene Symbol: TRA2A

Cytogenetic location: 7p15.3   Genomic coordinates (GRCh38) : 7:23,504,780-23,531,981 (from NCBI)


TEXT

Cloning and Expression

Dauwalder et al. (1996) reported the identification of TRA2-alpha (TRA2A), a human homolog of the Drosophila transformer-2 (tra2) protein. In Drosophila, the tra2 protein, in combination with the transformer (tra) protein, directs sex-specific splicing of pre-mRNA from the sex determination gene doublesex (dsx). Two alternative types of TRA2A cDNA clones were identified; each type encodes a different protein isoform with striking organizational similarity to Drosophila tra2 proteins. When expressed in flies, one TRA2-alpha isoform partially replaced the function of Drosophila tra2, affecting both female sexual differentiation and alternative splicing of dsx pre-mRNA. Like Drosophila tra2, the ability of TRA2-alpha to regulate dsx was female-specific and depended on the presence of the dsx splicing enhancer. These results demonstrated that TRA2-alpha has conserved a striking degree of functional specificity during evolution and suggested to Dauwalder et al. (1996) that, although they are likely to serve different roles in development, the TRA2 products of flies and humans have similar molecular functions.


Gene Function

Tacke et al. (1998) showed that human TRA2A and TRA2B (602719) proteins are present in HeLa cell nuclear extracts and that they bind efficiently and specifically to a previously characterized pre-mRNA splicing enhancer element. Both purified proteins bind preferentially to RNA sequences containing GAA repeats, characteristic of many enhancer elements. Neither TRA2 protein functions in constitutive splicing in vitro, but both activate enhancer-dependent splicing in a sequence-specific manner and restore it after inhibition with competitor RNA. These findings indicate that mammalian TRA2 proteins are sequence-specific splicing activators that are likely to participate in the control of cell-specific splicing patterns.


Mapping

Gross (2014) mapped the TRA2A gene to chromosome 7p15.3 based on an alignment of the TRA2A sequence (GenBank AB097048) with the genomic sequence (GRCh37).


REFERENCES

  1. Dauwalder, B., Amaya-Manzanares, F., Mattox, W. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proc. Nat. Acad. Sci. 93: 9004-9009, 1996. [PubMed: 8799144, related citations] [Full Text]

  2. Gross, M. B. Personal Communication. Baltimore, Md. 4/21/2014.

  3. Tacke, R., Tohyama, M., Ogawa, S., Manley, J. L. Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing. Cell 93: 139-148, 1998. [PubMed: 9546399, related citations] [Full Text]


Contributors:
Matthew B. Gross - updated : 04/21/2014
Creation Date:
Stylianos E. Antonarakis : 6/12/1998
carol : 03/05/2020
mgross : 04/21/2014
carol : 10/14/2013
mgross : 3/8/1999
carol : 6/16/1998

* 602718

TRANSFORMER 2 ALPHA HOMOLOG; TRA2A


Alternative titles; symbols

TRANSFORMER 2, DROSOPHILA, HOMOLOG OF, ALPHA


HGNC Approved Gene Symbol: TRA2A

Cytogenetic location: 7p15.3   Genomic coordinates (GRCh38) : 7:23,504,780-23,531,981 (from NCBI)


TEXT

Cloning and Expression

Dauwalder et al. (1996) reported the identification of TRA2-alpha (TRA2A), a human homolog of the Drosophila transformer-2 (tra2) protein. In Drosophila, the tra2 protein, in combination with the transformer (tra) protein, directs sex-specific splicing of pre-mRNA from the sex determination gene doublesex (dsx). Two alternative types of TRA2A cDNA clones were identified; each type encodes a different protein isoform with striking organizational similarity to Drosophila tra2 proteins. When expressed in flies, one TRA2-alpha isoform partially replaced the function of Drosophila tra2, affecting both female sexual differentiation and alternative splicing of dsx pre-mRNA. Like Drosophila tra2, the ability of TRA2-alpha to regulate dsx was female-specific and depended on the presence of the dsx splicing enhancer. These results demonstrated that TRA2-alpha has conserved a striking degree of functional specificity during evolution and suggested to Dauwalder et al. (1996) that, although they are likely to serve different roles in development, the TRA2 products of flies and humans have similar molecular functions.


Gene Function

Tacke et al. (1998) showed that human TRA2A and TRA2B (602719) proteins are present in HeLa cell nuclear extracts and that they bind efficiently and specifically to a previously characterized pre-mRNA splicing enhancer element. Both purified proteins bind preferentially to RNA sequences containing GAA repeats, characteristic of many enhancer elements. Neither TRA2 protein functions in constitutive splicing in vitro, but both activate enhancer-dependent splicing in a sequence-specific manner and restore it after inhibition with competitor RNA. These findings indicate that mammalian TRA2 proteins are sequence-specific splicing activators that are likely to participate in the control of cell-specific splicing patterns.


Mapping

Gross (2014) mapped the TRA2A gene to chromosome 7p15.3 based on an alignment of the TRA2A sequence (GenBank AB097048) with the genomic sequence (GRCh37).


REFERENCES

  1. Dauwalder, B., Amaya-Manzanares, F., Mattox, W. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proc. Nat. Acad. Sci. 93: 9004-9009, 1996. [PubMed: 8799144] [Full Text: https://doi.org/10.1073/pnas.93.17.9004]

  2. Gross, M. B. Personal Communication. Baltimore, Md. 4/21/2014.

  3. Tacke, R., Tohyama, M., Ogawa, S., Manley, J. L. Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing. Cell 93: 139-148, 1998. [PubMed: 9546399] [Full Text: https://doi.org/10.1016/s0092-8674(00)81153-8]


Contributors:
Matthew B. Gross - updated : 04/21/2014

Creation Date:
Stylianos E. Antonarakis : 6/12/1998

Edit History:
carol : 03/05/2020
mgross : 04/21/2014
carol : 10/14/2013
mgross : 3/8/1999
carol : 6/16/1998