The Investigation On The Role Of Metastasis-associated Genel(MTA1)in Regulating MRNA Alternative Splicing

Objective mRNA alternative splicing leads to the complexity and variarity of biological activities in higher organisms. Up to date, the investigation on the mRNA post-transcriptional processing is just on the starting line. Our pilot studies have shown that metastasis-associated 1 (MTA1) was observed binding to a mass of RNA-regulating proteins throughout the entire mRNA processing, distributing in nucleolus, nucleus, cytoplasm, ribosomes and RNA particles and granules. Base on above clues, we explored the global role of MTA1 in mRNA splicing and its potential effects on biological functions in cancer process.Methods Big data analysis was utilized to determine whether MTA1 was involved in the regulation of RNA splicing process; Molecular biology and cytobiology techniques combined with RNA sequencing were applied to determine the impact of MTA1 on transcriptome alternative splicing; CLIP-seq (crosslinking-immunprecipitation and high-throughput sequencing) technique and obtainable network data were adopted to analyze the possible mechanisms and relevant motifs of MTA1-involved mRNA splicing process. Data from multi-omics combined with immune interation techniques were intergrated to further refine the biological functions and therefore the mechanisms of RNA splicing process exerted by MTA1.Results Big data analysis confirmed the involvement of MTA1 in RNA splicing process in a series of cancer types. The geneset underwent alternative splicing regulated by MTA1 was extracted from the RNA-seq and CLIP-seq data, demonstrating the extensive role in mRNA splicing regulation and the broad capacity of RNA binding. Key moleculars involved in MTA1-mediated RNA regulation were screened by multi-omics combined with immune interation techniques, revealing the synergistic effect of PTBP1 with MTA1 in regulating mRNA alternative splicing.Conclusions MTA1 is a RNA binding protein, regulating mRNA alternative splicing in multiple types of tumors and broadly affecting the alternative splicing status of trascriptomes. Genes enriched by MTA1-regulated alternative spicing were involved in the regulation of cell cycle, metabolism, macromolecular transportation, RNA splicing, etc. MTA1 was likely to implement its function of extensively regulating the alternative splicing model via combining to pre-mRNA indirectly, the realization of which partly depended on PTBP1.