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XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265.

ABSTRACT: Pre-mRNA splicing is performed by the spliceosome. SR proteins in this macromolecular complex are essential for both constitutive and alternative splicing. By using the SR-related protein ZNF265 as bait in a yeast two-hybrid screen, we pulled out the uncharacterized human protein XE7, which is encoded by a pseudoautosomal gene. XE7 had been identified in a large-scale proteomic analysis of the human spliceosome. It consists of two different isoforms produced by alternative splicing. The arginine/serine (RS)-rich region in the larger of these suggests a role in mRNA processing. Herein we show for the first time that XE7 is an alternative splicing regulator. XE7 interacts with ZNF265, as well as with the essential SR protein ASF/SF2. The RS-rich region of XE7 dictates both interactions. We show that XE7 localizes in the nucleus of human cells, where it colocalizes with both ZNF265 and ASF/SF2, as well as with other SR proteins, in speckles. We also demonstrate that XE7 influences alternative splice site selection of pre-mRNAs from CD44, Tra2-beta1 and SRp20 minigenes. We have thus shown that the spliceosomal component XE7 resembles an SR-related splicing protein, and can influence alternative splicing.

SUBMITTER: Mangs AH

PROVIDER: S-EPMC1635291 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Our previous study revealed that microRNA (miR) ?30c represents a potential tumor suppressor gene, the expression of which is associated with decreased oncogenic potential in prostate cancer (PCa) cell lines. However, the functional role and underlying mechanisms of miR?30c in PCa remain to be fully elucidated. Reverse transcription?quantitative polymerase chain reaction and immunohistochemical analysis were used to detect the expression levels of alternative splicing factor/splicing factor 2 (ASF/SF2) in PCa tissues. A luciferase reporter assay was used to investigate whether ASF/SF2 may be a direct target gene of miR?30c. In addition, the effects of miR?30c on the proliferation and apoptosis of PCa cell lines were examined, following transfection with miR?30c mimics. Furthermore, correlation analysis was performed to investigate the relationship between the expression of miR?30c and ASF/SF2 and various clinicopathological parameters of patients with PCa. The present results demonstrated that PCa tissues exhibited higher levels of alternative splicing factor/splicing factor 2 (ASF/SF2), compared with normal tissues. In addition, miR?30c was revealed to targete the 3'?untranslated region of the ASF/SF2 gene, causing a decrease in the mRNA and protein levels of ASF/SF2. Furthermore, miR?30c was reported to decrease cell proliferation, increase the percentage of cells in the G1 cell cycle phase, and promote apoptosis through the inhibition of ASF/SF2. Following correlation analysis using patient samples, the expression of ASF/SF2 was revealed to be tightly correlated with the pathological stage of PCa and biochemical recurrence (BCR). In addition, patients with PCa exhibiting low expression levels of miR?30c and high expression of ASF/SF2 had significantly lower rates of BCR?free survival. In conclusion, the present study suggested that the tumor suppressor miR?30c may be involved in PCa tumorigenesis, possibly via targeting ASF/SF2. The combined analysis of the expression of ASF/SF2 and miR?30c may be a valuable tool for early prediction of BCR in patients with PCa following radical prostatectomy.

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XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265.

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