Drosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron
- 24 February 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (8), 2577-2582
- https://doi.org/10.1073/pnas.0812826106
Abstract
During Drosophila embryogenesis, the transcription factor Prospero is critical for neuronal differentiation and axonal outgrowth. The prospero pre-mRNA undergoes alternative splicing, but is unique in that it harbors a rare twintron whereby one intron lies embedded within another. The innermost intron is excised by the major U2-type spliceosome and the outermost is excised by the minor U12-type spliceosome. Previously, an intronic purine-rich element (PRE) was identified as an enhancer of both U2- and U12-type splicing, with a greater effect on the U2-type pathway. We find that the PRE binds Drosophila homologs of heterogeneous nuclear ribonucleoprotein (hnRNP) A1, Hrp38 and Hrp36. RNAi-mediated knockdown of these proteins in S2 cells specifically decreases U2-type splicing of the twintron, which is surprising because hnRNPs usually are repressive. Conversely, tethering Hrp38 to the twintron increases U2-type splicing. Thus, developmentally regulated alternative splicing of the prospero twintron can be explained by documented changes in the abundance of these hnRNP A1-like proteins during embryogenesis.This publication has 54 references indexed in Scilit:
- Heterogeneous Ribonucleoprotein M Is a Splicing Regulatory Protein That Can Enhance or Silence Splicing of Alternatively Spliced ExonsOnline Journal of Public Health Informatics, 2007
- PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytesNucleic Acids Research, 2007
- Spatio-temporal expression of Prospero is finely tuned to allow the correct development and function of the nervous system in Drosophila melanogasterDevelopmental Biology, 2007
- Intronic Binding Sites for hnRNP A/B and hnRNP F/H Proteins Stimulate Pre-mRNA SplicingPLoS Biology, 2006
- Dephosphorylation Shows SR Proteins the Way OutMolecular Cell, 2005
- SRprises along a Messenger’s JourneyMolecular Cell, 2005
- An Intronic Enhancer Regulates Splicing of the Twintron of Drosophila melanogaster prospero Pre-mRNA by Two Different SpliceosomesMolecular and Cellular Biology, 2004
- hnRNP PROTEINS AND THE BIOGENESIS OF mRNAAnnual Review of Biochemistry, 1993
- Cloning of the Drosophila prospero gene and its expression in ganglion mother cellsBiochemical and Biophysical Research Communications, 1992
- Studies of the strand-annealing activity of mammalian hnRNP complex protein A1Biochemistry, 1990