Hsa_circ_001988 has been identified as a tumor suppressor gene in several carcinomas. However, its expression pattern and role in gastric cancer (GC) have still remained elusive. This study aimed to explore the functions of hsa_circ_001988 in GC. Quantitative reverse transcription polymerase chain reaction assay was performed to assess the expressions of hsa_circ_001988, miR-197-3p, FBXW7, CCDC6, and U2AF65 in GC tissues. The correlation analysis was undertaken to find out the relationship between hsa_circ_001988 expression and clinicopathological factors. A series of cellular experiments were carried out to describe the effects of hsa_circ_001988 on GC in vivo and in vitro. Besides, RNA immunoprecipitation (RIP) assay was performed to verify the relationship among EIF4A3, U2AF65, and hsa_circ_001988. We first found that the expression of hsa_circ_001988 was decreased in 341 GC patients that was related to World Health Organization histological types, Lauren types, and tumor invasion depth (p < .05). Silencing of hsa_circ_001988 facilitated proliferation, colony formation, migration, and invasion of GC cells, while overexpression of hsa_circ_001988 reversed the effect on GC progression in vitro. Additionally, the results of subcutaneous xenotransplanted tumor model demonstrated that overexpressing hsa_circ_001988 significantly suppressed the subcutaneous tumor growth in vivo. Mechanistically, hsa_circ_001988 attenuated the miR-197-3p expression possibly due to its molecular sponge effect, and then, positively promoted FBXW7 expression. Afterwards, FBXW7 regulated the expressions of yes-associated protein 1, cyclinD1, CCDC6, and EMT-related proteins. Notably, RIP assay showed the enrichment relationship among EIF4A3, U2AF65, and hsa_circ_001988. Additionally, EIF4A3 or U2AF65 promoted cyclization of hsa_circ_001988 in GC. Hsa_circ_001988 inhibits the proliferation and metastasis of GC via modulating EIF4A3/U2AF65-mediated hsa_circ_001988/miR-197-3p/FBXW7 axis.

U2 snRNP auxiliary factor 65 kDa (U2AF65) is a splicing factor that promotes prespliceosome assembly. The function of U2AF65 in alternative splicing has been identified; however, the essential physiological role of U2AF65 remains poorly understood. In this study, we investigated the regulatory role of U2AF65 in milk synthesis and growth of bovine mammary epithelial cells (BMECs). Our results showed that U2AF65 localizes in the nucleus. Treatment with amino acids (Met and Leu) and hormones (prolactin and β-estradiol) upregulated the expression of U2AF65 in these cells. U2AF65 overexpression increased the synthesis of β-casein, triglycerides, and lactose; increased cell viability; and promoted proliferation of BMECs. Furthermore, our results showed that U2AF65 positively regulated mTOR phosphorylation and expression of mature mRNA of mTOR and SREBP-1c. Collectively, our findings demonstrate that U2AF65 regulates the mRNA expression of signalling molecules (mTOR and SREBP-1c) involved in milk synthesis and growth of BMECs, possibly via controlling the splicing and maturation of these mRNAs. U2 snRNP auxiliary factor 65 kDa (U2AF65) is a splicing factor that promotes prespliceosome assembly. The essential physiological role of U2AF65 remains poorly understood. In the present study, we confirmed that U2AF65 functions as a positive regulator of milk synthesis in and proliferation of bovine mammary epithelial cells via the mTOR-SREBP-1c signalling pathway. Therefore, our study uncovers the regulatory role of U2AF65 in milk synthesis and cell proliferation.

RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood.
In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells.
RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5\' and 3\' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65.
RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.
The current study offers a genome-wide view of RBM39\'s regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels.

U2 snRNP auxiliary factor 65 kDa (U2AF(65)) is a general splicing factor that contacts polypyrimidine (Py) tract and promotes prespliceosome assembly. In this report, we show that U2AF(65) stimulates alternative exon skipping in spinal muscular atrophy (SMA)-related survival motor neuron (SMN) pre-mRNA. A stronger 5\' splice-site mutation of alternative exon abolishes the stimulatory effects of U2AF(65). U2AF(65) overexpression promotes its own binding only on the weaker, not the stronger, Py tract. We further demonstrate that U2AF(65) inhibits splicing of flanking introns of alternative exon in both three-exon and two-exon contexts. Similar U2AF(65) effects were observed in Fas (Apo-1/CD95) pre-mRNA. Strikingly, we demonstrate that U2AF(65) even inhibits general splicing of adenovirus major late (Ad ML) or β-globin pre-mRNA. Thus, we conclude that U2AF(65) possesses a splicing Inhibitory function that leads to alternative exon skipping.