Journal Article

Alternative Splicing of TAF6: Downstream Transcriptome Impacts and Upstream RNA Splice Control Elements

Benecke, Arndt G., Kamtchueng, Catherine, Léger, Hélène, Bell, Brendan, Delannoy, Aurélie, Wilhelm, Emmanuelle, Stébenne, Marie-Éve

2014

Overview

The TAF6δ pathway of apoptosis can dictate life versus death decisions independently of the status of p53 tumor suppressor. TAF6δ is an inducible pro-apoptotic subunit of the general RNA polymerase II (Pol II) transcription factor TFIID. Alternative splice site choice of TAF6δ has been shown to be a pivotal event in triggering death via the TAF6δ pathway, yet nothing is currently known about the mechanisms that promote TAF6δ splicing. Furthermore the transcriptome impact of the gain of function of TAF6δ versus the loss of function of the major TAF6α splice form remains undefined. Here we employ comparative microarray analysis to show that TAF6δ drives a transcriptome profile distinct from that resulting from depletion of TAF6α. To define the cis-acting RNA elements responsible for TAF6δ alternative splicing we performed a mutational analysis of a TAF6 minigene system. The data point to several new RNA elements that can modulate TAF6δ and also reveal a role for RNA secondary structure in the selection of TAF6δ.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alternative Splicing / Analysis / Apoptosis / Biology and life sciences / Cancer / Cellular biology / Deoxyribonucleic acid / DNA / DNA microarrays / DNA-directed RNA polymerase / Exons / Gene expression / Gene Silencing / HeLa Cells / Human health and pathology / Humans / Life Sciences / Mutation / Nucleic Acid Conformation / p53 Protein / Protein structure / Ribonucleic acid / RNA / RNA - chemistry / RNA - genetics / RNA polymerase / RNA polymerase II / RNA, Small Interfering - genetics / Secondary structure / TATA-Binding Protein Associated Factors - genetics / TFIID protein / Transcriptome / Tumor proteins / Tumor suppressor genes