Work

The Ig Heavy Chain 3′ End Confers a Posttranscriptional Processing Advantage to Bcl-2–IgH Fusion RNA in t(14;18) Lymphoma

Year: 1998

Type: article

Abstract: The chromosomal translocation t(14;18) in lymphoma leads to an overproduction of the Bcl-2 protein on the basis of increased Bcl-2 mRNA levels. Whereas the juxtaposition of Bcl-2 with the Ig heavy chain locus causes a transcriptional activation, 70% of the lymphomas also produce Bcl-2-Ig fusion RNAs with Ig 3' ends. Using S1 nuclease protection assays that can discriminate between nuclear RNA precursors and spliced mRNA, we found that the fusion RNAs in t(14;18) cell lines exhibit an additional posttranscriptional processing advantage. Transfection experiments with artificial genes containing various Bcl-2 or Ig 3' ends show that this effect is (1) related to RNA splicing and/or nucleocytoplasmic transport; (2) independent of transcriptional activation by the heavy chain enhancer; (3) dependent on the presence of the JH-CH and C-gamma1 Ig introns; and (4) tissue specific for B cells. This constitutes a novel mechanism of oncogene deregulation unrelated to transcriptional activation or half-life prolongation. The data further support the existence of a tissue-specific posttranscriptional pathway of Ig regulation in B cells.

Source: Blood

DOI: 10.1182/blood.v91.10.3952

Authors: Alexander Scheidel Petrovic, Robert L. Young, Bernadette Hilgarth, Peter Ambros, Stanley J. Korsmeyer, Ulrich Jaeger