Identification of a novel cis-element that regulates alternative splicing of Bcl-x pre-mRNA

Jaehoon Lee, Jianhua Zhou, Xuexiu Zheng, Sunghee Cho, Heegyum Moon, Tiing Jen Loh, Kyungjin Jo, Haihong Shen

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Alternative splicing plays an important role in the control of apoptosis. A number of genes related to apoptosis undergo alternative splicing. Among them, the apoptotic regulator Bcl-x produces two major isoforms, Bcl-xL and Bcl-xS, through the alternative splicing of exon 2 in its pre-mRNA. These isoforms have antagonistic function in apoptotic pathway; Bcl-xL is pro-apoptotic, while Bcl-xS is anti-apoptotic. The balanced ratio of two isoforms is important for cell survival. However, regulatory mechanisms of Bcl-x splicing remain poorly understood. Using a mini-gene system, we have found that a 105. nt exonic region (E3b) located within exon 3 affects exon 2 splicing in the Bcl-x gene. Further deletion and mutagenesis studies demonstrate that this 105. nt sequence contains various functional elements which promote skipping of exon 2b. One of these elements forms a stem-loop structure that stimulates skipping of exon 2b. Furthermore our results prove that the stem-loop structure functions as an enhancer in general pre-mRNA splicing. We conclude that we have identified a cis-regulatory element in exon 3 that affects splicing of exon 2 in the Bcl-x gene. This element could be potentially targeted to alter the ratio of Bcl-xL and Bcl-xS for treatment of tumors through an apoptotic pathway.

Original languageEnglish
Pages (from-to)467-472
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number2
DOIs
Publication statusPublished - 6 Apr 2012
Externally publishedYes

Keywords

  • Alternative splicing
  • Apoptosis
  • Bcl-x
  • Exon inclusion
  • Exon skipping
  • Pre-mRNA splicing

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