RNA BINDING PROTEIN - ALTERNATIVE SPLICING ANALYSIS OF ABERRANT ALTERNATIVE SPLICING EVENTS IN OSTEOARTHRITIS

Abstract

Background: Osteoarthritis (OA), the most common degenerative joint disorder, is characterized by cartilage destruction. Alternative splicing (AS) is an important process that yields structurally and functionally distinct mRNAs and protein variants. Several studies have suggested that AS is mostly modulated by RNA-binding proteins. They play important roles in the pathogenesis and process. Methods: We extracted transcriptome data from GSE111358, which contains 10 OA samples and six control samples. We then performed a systematic analysis of the data to obtain RNA-binding proteins and differential AS mRNAs that were aberrantly expressed in OA. Six femoral head cartilage samples were collected from three patients with OA and three femoral neck of fracture patients who underwent hip replacement. qRT-PCR of tissue RNA was conducted to verify this finding. Results: Eighty-six differentially expressed RNA-binding proteins and 5231 differentially expressed AS events were identified. We constructed an RNA binding protein-AS regulatory network, by which we found that four genes (OGN, CD44, CD55, and ZFP36L1) were associated with aberrant AS events and OA. qPCR experiments showed that CD44 and ZFP36L1 mRNA were expressed at lower levels in OA cartilage. Conclusions: We constructed a RBP-AS co-expression network in OA cartilage based on transcriptome RNA-seq data. ZFP36L1 and CD44 expression levels were significantly lower in OA cartilage. Thus, they may regulate RARG alternative splicing and postpone OA progression.