Open AccessDrosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron
Author(s) -
Sumit Borah,
Anthony Wong,
Joan A. Steitz
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0812826106
Subject(s) - rna splicing , spliceosome , intron , exonic splicing enhancer , biology , ribonucleoprotein , snrnp , heterogeneous nuclear ribonucleoprotein , alternative splicing , microbiology and biotechnology , drosophila melanogaster , genetics , small nuclear ribonucleoprotein , enhancer , exon , splicing factor , rna , transcription factor , gene
DuringDrosophila embryogenesis, the transcription factor Prospero is critical for neuronal differentiation and axonal outgrowth. Theprospero 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 bindsDrosophila 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 theprospero twintron can be explained by documented changes in the abundance of these hnRNP A1-like proteins during embryogenesis.