[WASH regulates alternative splicing and gene transcription by interacting with hnRNP A1]

Objective To investigate the interaction between Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and its biological functions. Methods The interaction between WASH/FAM21, the core member of WASH complex, and hnRNP A1 was identified by mass spectrometry and co-immunoprecipitation. Telomere lengths of shWASH and shScramble cells were measured by Real-time qPCR. RNA-seq was used to generate the transcription profiles of shWASH and shScramble cells. Results Mass spectrometry results indicated that a variety of hnRNP family members, including hnRNP A1, interact with FAM21-d219N. The interaction between endogenous WASH/FAM21 and hnRNP A1 was confirmed by co-immunoprecipitation results. Depletion of WASH did not affect the relative length of telomeres, but it significantly increased the exon skipping and led to the variation of transcriptional expression of hundreds of genes, including some NF-κB target genes. Conclusion WASH in the nucleus interacts with hnRNP A1 to participate in the regulation of alternative splicing and gene transcription.