title: Identification of a novel cis-element that regulates alternative splicing of Bcl-x pre-mRNA.
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.
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
authors.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Jo
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D012322:RNA Precursors / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D012322:RNA Precursors; D051020:bcl-X Protein