SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster

Abstract

BackgroundThe SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.ResultsWe have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.ConclusionsWe have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes.

Inhibition of polyadenylation reduces inflammatory gene induction

“…Termination is influenced by the rate of transcription elongation, by the efficiency of cleavage and polyadenylation, as well as by sequences found in the terminator region and in the promoter, giving rise to gene-specific effects on termination rates (Banerjee et al 2009;West and Proudfoot 2009;Milcarek et al 2011;Mukundan and Ansari 2011). Recently, five research groups reported that the induction of specific mRNAs by transcription factors and their associated transacting factors are mediated to a significant extent by effects on cleavage, polyadenylation, and transcription termination (Chipumuro and Henriksen 2011;Milcarek et al 2011;Mukundan and Ansari 2011;Nagaike et al 2011;Waldholm et al 2011). One of these studies describes STAT1-mediated recruitment of polyadenylation factors to the IRF1 gene through chromatin modification of the terminator region of this gene (Chipumuro and Henriksen 2011).…”

Brahma regulates a specific trans-splicing event at themod(mdg4)locus ofDrosophila melanogaster

“…18 The BRM protein of D. melanogaster also affects pre-mRNA processing, and depletion of BRM changes the relative abundances of a subset of alternatively processed transcripts in D. melanogaster. 19,20 A fraction of BRM is associated with nascent pre-mRNPs, which suggests that SWI/SNF affects pre-mRNA processing by acting at the RNA level. 19 One of the genes whose expression is modulated by the levels of BRM in D. melanogaster is mod(mdg4).…”

“…19 One of the genes whose expression is modulated by the levels of BRM in D. melanogaster is mod(mdg4). 19,20 The mod(mdg4) gene codes for insulator proteins that participate in the establishment and maintenance of chromatin domains. 6 The mod(mdg4) gene produces 31 splicing isoforms that share a common N-terminal sequence, but have different C-terminal regions.…”

“…[18][19][20] SWI/SNF is an ATP-dependent, multi-subunit complex that regulates the transcription of many genes by remodeling nucleosomes at promoter regions. [21][22][23] The Brahma (BRM) protein is the only ATPase subunit of the SWI/ SNF complex in D. melanogaster.…”

SWI/SNF Chromatin Remodeling Complex Involved in RNA Polymerase II Elongation Process in Drosophila melanogaster

“…The knockdown of core Drosophila melanogaster SWI/SNF (dSWI/SNF) subunits has been shown to facilitate the alternative splicing of several Drosophila genes both in culturing cells and in the larvae [9]. Recently, physical association of the SWI/SNF complex with pre-mRNP of Chironomus tentans was demonstrated both biochemically and by immuneelectron microscopy [10].…”