Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators.

Several apoptotic regulators, including Bcl-x, are alternatively spliced to produce isoforms with opposite functions. We have used an RNA interference strategy to map the regulatory landscape controlling the expression of the Bcl-x splice variants in human cells. Depleting proteins known as core (Y14 and eIF4A3) or auxiliary (RNPS1, Acinus, and SAP18) components of the exon junction complex (EJC) improved the production of the proapoptotic Bcl-x(S) splice variant.

TCERG1 regulates alternative splicing of the Bcl-x gene by modulating the rate of RNA polymerase II transcription.

Complex functional coupling exists between transcriptional elongation and pre-mRNA alternative splicing. Pausing sites and changes in the rate of transcription by RNA polymerase II (RNAPII) may therefore have fundamental impacts in the regulation of alternative splicing. Here, we show that the elongation and splicing-related factor TCERG1 regulates alternative splicing of the apoptosis gene Bcl-x in a promoter-dependent manner.

The DNA damage response pathway regulates the alternative splicing of the apoptotic mediator Bcl-x.

Alternative splicing often produces effectors with opposite functions in apoptosis. Splicing decisions must therefore be tightly connected to stresses, stimuli, and pathways that control cell survival and cell growth. We have shown previously that PKC signaling prevents the production of proapoptotic Bcl-x(S) to favor the accumulation of the larger antiapoptotic Bcl-x(L) splice variant in 293 cells.

[Guiding and integrating to control and diversify splicing].

Recent studies directed at understanding alternative splicing control have produced an expanding list of regulators that can enhance or silence the use of splice sites by binding to specific sequences. A fine balance in the expression and the combinatorial use of these factors would help to adapt splicing decisions to a variety of situations. Additional levels of control are provided by tightly connecting the activity of alternative splicing factors with other cellular processes such as signal transduction and transcription.