Integrative RNA-seq and iRIP-seq analysis links SNRPA overexpression to transcriptomic and splicing alterations in...

Small Nuclear Ribonucleoprotein Polypeptide A (SNRPA), an RNA-binding protein associated with HCC survival, emerges as a key regulator requiring mechanistic study.

To delineate SNRPA's functions, we generated SNRPA-overexpressing HepG2 cells and performed RNA-seq to identify SNRPA-regulated transcripts and alternative splicing events(RASEs). Improved RNA Immunoprecipitation Sequencing (iRIP-seq) mapped RNA interactomes, combined with integrative bioinformatics to define SNRPA-bound RNAs and splicing targets.

RNA-seq revealed extensive transcriptomic alterations driven by SNRPA overexpression, including 498 differentially expressed genes(DEGs) and 2316 RASEs. iRIP-seq identified a subset of SNRPA-bound transcripts that also exhibited changes in expression and/or alternative splicing upon SNRPA overexpression, and many of these genes have been previously implicated in hepatocellular carcinoma (HCC)-related biological processes. Among the 498 DEGs identified, 12 RNA-binding proteins (RBPs) with known roles in HCC were found to be regulated by SNRPA overexpression, including PCBP2, HNRNPH1, and EIF4A2; these RBPs are involved in alternative splicing, mRNA stability and translational regulation, and their dysregulation further expands the regulatory network of SNRPA in HCC. Functional annotation of these overlapping genes indicated enrichment in pathways related to RNA processing, transcription-related processes, and cell division. SNRPA may play dual roles in RNA transcript binding and the regulation of splicing, particularly in pathways associated with tumorigenesis and cellular proliferation.

These findings suggest that SNRPA overexpression is associated with HCC progression-related transcriptomic and splicing alterations, and may be involved in HCC progression through regulating the expression of DEGs and the splicing patterns of carcinogenic targets, with direct causal effects requiring further functional validation.