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HnRNP A2/B1 regulates alternative splicing of Tid1 isoforms (742.1)
Author(s) -
Chen ChiYuan,
Chuang YenShu,
Pi WenChieh,
Wang TzuChien
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.742.1
Subject(s) - rna splicing , heterogeneous nuclear ribonucleoprotein , heterogeneous ribonucleoprotein particle , alternative splicing , exon , exonic splicing enhancer , gene knockdown , biology , microbiology and biotechnology , jurkat cells , intron , gene , genetics , rna , t cell , immune system
Tid1, a DnaJ cochaperone, may promote degradation of oncogenic kinases. Tid1 is composed of 12 exons separated by 11 introns. Two alternatively spliced forms of Tid1 are expressed in humans, Tid1‐L and Tid1‐S. The Tid1‐S is generated by splicing of exon 10 to exon 12. Overexpression of Tid1‐S and Tid1‐L has been shown to produce opposing effects: cell death is repressed by Tid1‐S and enhanced by Tid1‐L. However, the mechanism of alternative splicing regulators to Tid1 isoforms development has been largely unknown. Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a large family of proteins that associate with nascent pre‐mRNAs, packaging them into hnRNP particles. The A/B subfamily of hnRNPs (hnRNP A/Bs) are the most abundant hnRNPs in the nucleus. hnRNP A2/B1 is critical for precursor messenger RNA splicing. In this study, we tested the postulation that hnRNP A2/B1 may regulate alternative splicing of Tid1 isoforms. Our preliminary results indicated that knockdown of hnRNP A2/B1 in acute T cell leukemia‐derived Jurkat cells and lung cancer cells increased the expression of Tid1‐L gene and protein. Moreover, knockdown of hnRNP A2 produced a significant inhibition of cellular proliferation in Jurkat cells. These results suggest that specific knockdown for hnRNP A2/B1 decreases exclusion of exons 11 of Tid1 pre‐mRNA and influence cell proliferation of human cancer cells.