Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas

Suryaprabha Chunduru, Hiroyuki Kawami, Richard Gullick, William J. Monacci, Gerard Dougherty, Mary Lou Cutler

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies demonstrated that the Ras suppressor, RSU-1, localizes to human chromosome 10p13, a region frequently deleted in high grade gliomas, and that RSU-1 expression inhibited the tumorigenesis of a glioblastoma cell line. We have now examined RNA from human glial tumors for RSU-1 expression by RT-PCR using primers for the 5′ and 3′ ends of the RSU-1 open reading frame. Analysis of the amplified RSU-1 cDNA demonstrated that in addition to the entire 858 by RSU-1 open reading frame, a shorter 725 bp RSU-1 fragment was amplified as well. Sequencing of this product revealed that it encoded a RSU-1 cDNA product which was missing a single 133 bp internal exon. This exon-deleted product was found in 30% of the high grade gliomas studied and 2/3 oligodendrogliomas, but not in other CNS tumors, bladder or colon tumors or normal tissue. The exon-deleted RSU-1 product was infrequently detected in RNA from human tumor cell lines. Expression of an HA-tagged form of the deleted RSU-1 protein in transfected Cos 1 cells revealed that the protein was unstable, with a half life of less than 1 h, in contrast to the full length HA-tagged Rsu-1 protein which was stable for more than 4 h. These results suggest that the alternative splicing of the RSU-1 RNA to produce the exon-deleted from constitutes a mechanism for reduction or loss of functional Rsu-1. Because the expression of Rsu-1 can inhibit malignant growth of glioblastoma cells, the depletion of Rsu-1, via the production of the alternatively spliced form of RSU-1, may inhibit growth regulation in tumors.

Original languageEnglish (US)
Pages (from-to)201-211
Number of pages11
JournalJournal of neuro-oncology
Volume60
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • Exon skipping
  • Glioblastoma
  • Glioma
  • RNA
  • Rsu-1
  • Splicing

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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