Dataset reporting the differential effect of HNRNPA1 isoforms on alternative splicing

Heterogeneous nuclear ribonucleoprotein A1 (<i>HNRNPA1</i>) encodes two main protein coding variants: hnRNP A1 and hnRNP A1B. The isoforms differ by the exclusion or inclusion of exon 8 (sometimes referred to as exon 7B), which extends the length of the intrinsically disordered region (IDR). HnRNP A1 is implicated in most major steps of nascent RNA transcript processing, with RNA splicing being the most studied function. While hnRNP A1 has been studied extensively, little is known about the relevance of the longer isoform, hnRNP A1B. In fact, with respect to alternative splicing, only two groups have reported a functional analysis of both isoforms, revealing that both isoforms modulate alternative splicing, albeit with different efficiencies. To better understand the contribution of each isoform on alternative splicing, we analyzed the transcriptomes of mouse erythroleukemia cells either lacking <i>HNRNPA1</i> (CB3) or uniquely expressing one isoform [hnRNP A1 (CB3 A1) or hnRNP A1B (CB3 A1B)] via stable constitutive expression of murine cDNAs. Our data indicate that differential isoform expression modulates the splicing of both shared and isoform-specific gene sets. These genes are involved in a wide variety of molecular functions and biological processes. Finally, and intriguingly, analysis of the genes with the largest differences in inclusion levels revealed enrichment for genes implicated in several neurodegenerative and neurodevelopmental diseases, as well as intellectual disability, myopathy and cancer.