A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Han Wu; Shuying Sun; Kang Tu; Yuan Gao; Bin Xie; Adrian R. Krainer; Jun Zhu

doi:10.1016/j.molcel.2010.02.021

A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Han Wu, Shuying Sun, Kang Tu, Yuan Gao, Bin Xie, Adrian R. Krainer, Jun Zhu

Research output: Contribution to journal › Article › peer-review

129 Scopus citations

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.

Original language	English (US)
Pages (from-to)	67-77
Number of pages	11
Journal	Molecular cell
Volume	38
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2010.02.021
State	Published - Apr 9 2010
Externally published	Yes

Keywords

PROTEINS
RNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2010.02.021

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title = "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.",

keywords = "PROTEINS, RNA",

author = "Han Wu and Shuying Sun and Kang Tu and Yuan Gao and Bin Xie and Krainer, {Adrian R.} and Jun Zhu",

note = "Funding Information: We thank Drs. Sandeep Dave and Mariano Garcia-Blanco (Duke University Medical Center) for comments and critical reading of the manuscript. We are grateful to Drs. Uwe Ohler and Zhong Wang (Duke Institute for Genome Sciences and Policy) for valuable advice on computational analysis, and Mr. Matt Gemberling for constructing the mutant minigene reporters. This work was supported by the National Science Foundation (MCB 0822033 to J.Z.). ",

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AU - Sun, Shuying

AU - Tu, Kang

AU - Gao, Yuan

AU - Xie, Bin

AU - Krainer, Adrian R.

AU - Zhu, Jun

N1 - Funding Information: We thank Drs. Sandeep Dave and Mariano Garcia-Blanco (Duke University Medical Center) for comments and critical reading of the manuscript. We are grateful to Drs. Uwe Ohler and Zhong Wang (Duke Institute for Genome Sciences and Policy) for valuable advice on computational analysis, and Mr. Matt Gemberling for constructing the mutant minigene reporters. This work was supported by the National Science Foundation (MCB 0822033 to J.Z.).

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Y1 - 2010/4/9

N2 - 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.

AB - 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.

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A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Abstract

Keywords

ASJC Scopus subject areas

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