Project description:The Bronx waltzer mutation in Srrm4, a gene that encodes a neuronal Ser/Arg (SR)-rich splicing factor, disrupts the expression of several alternative exons specifically in the inner ear. Here we show that the expression of SRRM3 in neurons limits the distribution of SRRM4-dependent splicing. In vitro, SRRM3 and SRRM4 regulated the same alternative exons, yet in vivo Srrm3 deficiency caused neuronal splicing alterations and motor dysfunction, indicating that SRRM3 has non-redundant functions. Mice harboring mutations in both Srrm3 and Srrm4 failed to breathe, and their neuromuscular junctions (NMJ) were malformed. Transcriptome-wide analysis revealed a large network of SRRM3/SRRM4-dependent splicing changes, including the skipping of key exons in the NMJ organizer Agrin. Furthermore, SRRM3/SRRM4 regulated gene expression through neuron-specific switches in chromatin regulatory complexes and by altering the reading frame in several mRNAs. Our findings reveal that the SRRM3/SRRM4 subfamily of SR proteins is central to regulation of the neuronal transcriptome. In this dataset, we include probe-set level data obtained from brain cortex samples. The processed data represent probe-set intensities that have been normalized to gene expression levels.
Project description:The Bronx waltzer mutation in Srrm4, a gene that encodes a neuronal Ser/Arg (SR)-rich splicing factor, disrupts the expression of several alternative exons specifically in the inner ear. Here we show that the expression of SRRM3 in neurons limits the distribution of SRRM4-dependent splicing. In vitro, SRRM3 and SRRM4 regulated the same alternative exons, yet in vivo Srrm3 deficiency caused neuronal splicing alterations and motor dysfunction, indicating that SRRM3 has non-redundant functions. Mice harboring mutations in both Srrm3 and Srrm4 failed to breathe, and their neuromuscular junctions (NMJ) were malformed. Transcriptome-wide analysis revealed a large network of SRRM3/SRRM4-dependent splicing changes, including the skipping of key exons in the NMJ organizer Agrin. Furthermore, SRRM3/SRRM4 regulated gene expression through neuron-specific switches in chromatin regulatory complexes and by altering the reading frame in several mRNAs. Our findings reveal that the SRRM3/SRRM4 subfamily of SR proteins is central to regulation of the neuronal transcriptome. In this dataset, we include probe-set level data obtained from cerebellar samples. The processed data represent probe-set intensities that have been normalized to gene expression levels.
Project description:To investigate the role of MSI1, SRRM3 and SRRM4 as a regulator of retina microexons (RetMICs) in vitro in humans, we have ectopically expressed these genes in HEK293 cells and performed RNA-seq.
Project description:DRM complex mutant lin-54 vs. H3K36 methyltransferase mutant mes-4 vs. lin-54; mes-4 double mutant vs. wild type C.elegans germline
Project description:Transcription profiling of cerebellum cells from wild type mice or mice overexpressing TATA-binding protein (TBP) or a mutant version of TBP