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A splicing-independent function of SF2/ASF in microRNA processing.

ABSTRACT: Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upregulated microRNAs (miR-7) can form a negative feedback loop: SF2/ASF promotes miR-7 maturation, and mature miR-7 in turn targets the 3'UTR of SF2/ASF to repress its translation. Enhanced microRNA expression is mediated by direct interaction between SF2/ASF and the primary miR-7 transcript to facilitate Drosha cleavage and is independent of SF2/ASF's function in splicing. Other miRNAs, including miR-221 and miR-222, may also be regulated by SF2/ASF through a similar mechanism. These results underscore a function of SF2/ASF in pri-miRNA processing and highlight the potential coordination between splicing control and miRNA-mediated gene repression in gene regulatory networks.

SUBMITTER: Wu H

PROVIDER: S-EPMC3395997 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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A splicing-independent function of SF2/ASF in microRNA processing.

Wu Han H Sun Shuying S Tu Kang K Gao Yuan Y Xie Bin B Krainer Adrian R AR Zhu Jun J

Molecular cell 20100401 1

Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upregulated microRNAs (miR-7) can form a negative feedback loop: SF2/ASF promotes miR-7 maturation, and mature miR-7 in turn targets the 3'UTR of SF2/ASF to repress its translation. En ...[more]

PMID: 20385090

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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.

Dataset Information

A splicing-independent function of SF2/ASF in microRNA processing.

Publications

A splicing-independent function of SF2/ASF in microRNA processing.

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