Disease relevance of RBM4

• Our work also suggests that down-regulating tau exon 10 splicing activators, such as RBM4, may be of therapeutic potential in tauopathies involving excessive tau exon 10 inclusion [1].

High impact information on RBM4

• TRN-SR2 interacts specifically with RBM4 in a Ran-sensitive manner [2].
• Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB [3].
• This study suggests a possible mechanism underlying the regulated alternative splicing of alpha-TM by the antagonistic splicing regulators RBM4 and PTB [3].
• Using minigenes, we demonstrated that RBM4 can activate the selection of skeletal muscle-specific exons, possibly via binding to intronic pyrimidine-rich elements [3].
• Immunohistological analyses reveal that RBM4 is expressed in the human brain regions affected in tauopathy, including the hippocampus and frontal cortex [1].

Biological context of RBM4

• TRN-SR2 indeed mediates the nuclear import of a recombinant protein containing the RBM4 C-terminal domain [2].
• A putative intronic splicing enhancer located in intron 10 of the tau gene is required for the splicing stimulatory activity of RBM4 [1].
• In cells transfected with a tau minigene, RBM4 overexpression leads to an increased inclusion of exon 10, whereas RBM4 down-regulation decreases exon 10 inclusion [1].
• RBM4 conferred dose-dependent and cell-specific regulation of alternative splicing of pre-mRNAs transcribed from several reporter genes [4].

Physical interactions of RBM4

• WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo [4].

Other interactions of RBM4

• We conclude that the (+KTS) form of WT1 is able to inhibit the effect of RBM4 on alternative splicing [4].

Analytical, diagnostic and therapeutic context of RBM4

• Immunofluorescence imaging of full-length and mutated RBM4 revealed that the C-terminus of RBM4 is crucial for targeting to speckles [5].

References