The SR Protein 9G8 and the Wilms' Tumor Suppressor Protein WT1 Promote Translation of mRNAs with Retained Introns

Abstract

Recent data indicate that the various steps in post-transcriptional gene expression are linked. In the studies presented in this thesis, we show further evidence of the interconnection between the multiple steps of mRNA metabolism. In one study, we show a link between splicing with nucleocytoplasmic export and translation. In another study, we show that the products of an alternatively spliced pre-mRNA have different roles in mRNA metabolism. Specifically, SR proteins, Tap, and WT1(+KTS) function similarly to link nuclear and cytoplasmic events in the expression of mRNAs with retained introns.The first study examines the cytoplasmic role of the splicing regulatory SR protein, 9G8, which has recently been proposed to function in mRNA export in conjunction with the export protein, Tap/NXF1.We investigated the effect of 9G8 on cytoplasmic RNA fate. 9G8 was shown to enhance expression of unspliced RNA containing either the MPMV-CTE or the recently discovered Tap-CTE. 9G8 also enhanced polyribosome association of unspliced RNA containing a CTE. Hyperphosphorylated 9G8 was present in monosomes and small polyribosomes, whereas soluble fractions contained only hypophosphorylated