Identification of a novel cis-element that regulates alternative splicing of Bcl-x pre-mRNA

Lee, Jae‐Hoon; Zhou, Jianhua; Zheng, Xuexiu; Cho, Sunghee; Moon, Heegyum; Loh, Tiing Jen; Jo, Kyung-Jin; Shen, Haihong

doi:10.1016/j.bbrc.2012.03.029

Cited by 16 publications

(13 citation statements)

References 37 publications

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“…It was shown that alternative splicing regulates apoptosis by producing pro-apoptotic and anti-apoptotic isoforms from one pre-mRNA, as shown in Bcl-x, Fas and Caspase-2 pre-mRNAs [10, 11]. Anti-apoptotic pathways are essential for tumorigenesis and the resistance to cancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8

Jang

Loh

Choi

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Alternative splicing plays an important role in gene expression by producing different proteins from a gene. Caspase-2 pre-mRNA produces anti-apoptotic Casp-2S and proapoptotic Casp-2L proteins through exon 9 inclusion or skipping. However, the molecular mechanisms of exon 9 splicing are not well understood. Here we show that knockdown of SRp20 with siRNA induced significant increase of endogenous exon 9 inclusion. In addition, overexpression of SRp20 promoted exon 9 skipping. Thus we conclude that SRp20 promotes exon 9 skipping. In order to understand the functional target of SRp20 on caspase-2 premRNA, we performed substitution and deletion mutagenesis on the potential SRp20 binding sites that were predicted from previous reports. We demonstrate that substitution mutagenesis of the potential SRp20 binding site on exon 8 severely disrupted the effects of SRp20 on exon 9 skipping. Furthermore, with the approach of RNA pulldown and immunoblotting analysis we show that SRp20 interacts with the potential SRp20 binding RNA sequence on exon 8 but not with the mutant RNA sequence. In addition, we show that a deletion of 26 nt RNA from 5’ end of exon 8, a 33 nt RNA from 3’ end of exon 10 and a 2225 nt RNA from intron 9 did not compromise the function of SRp20 on exon 9 splicing. Therefore we conclude that SRp20 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8. Our results reveal a novel mechanism of Caspase-2 pre-mRNA splicing.

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Section: Introductionmentioning

confidence: 99%

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8

Jang

Loh

Choi

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…Abnormal regulation of alternative splicing causes a variety of human diseases including cancer [18]. Alternative splicing is finely regulated by cis-acting elements and trans-acting elements [19, 20]. Cis-acting elements are RNA sequences on pre-mRNA which function as either enhancer or inhibitor to regulate exon inclusion or skipping.…”

Section: Introductionmentioning

confidence: 99%

SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene

Moon

Cho

Loh

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The product of proto-oncogene Ron is a human receptor for the macrophage-stimulating protein (MSP). Upon activation, Ron is able to induce cell dissociation, migration and matrix invasion. Exon 11 skipping of Ron pre-mRNA produces Ron△165 protein that is constitutively active even in the absence of its ligand. Here we show that knockdown of SRSF2 promotes the decrease of exon 11 inclusion, whereas overexpression of SRSF2 promotes exon 11 inclusion. We demonstrate that SRSF2 promotes exon 11 inclusion through splicing and transcription procedure. We also present evidence that reduced expression of SRSF2 induce a decrease in the splicing of both intron 10 and 11, by contrast, overexpression of SRSF2 induce an increase in the splicing of intron 10 and 11. Through mutation analysis, we show that SRSF2 functionally target and physically interact with CGAG sequence on exon 11. In addition, we reveal that weak strength of splice sites of exon 11 is not required for the function of SRSF2 on the splicing of Ron exon 11. Our results indicate that SRSF2 promotes exon 11 inclusion of Ron proto-oncogene through targeting exon 11. Our study provides a novel mechanism by which Ron is expressed.

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“…Splicing signals, such as the 5'-splice site, 3'-splice site, branch point, and polypyrimidine tract site, are required for pre-mRNA splicing (Lee et al, 2012). Additional RNA sequence elements, such as exon splicing enhancers, are also important to initiate the pre-mRNA splicing of many genes.…”

Section: Exon Splicing Enhancer Prediction Of the Two Transcriptsmentioning

confidence: 99%

Identification and characterization of a novel splice variant of the PLCζ1 gene in bull testis tissues

Pan

Zhang

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Phospholipase C zeta 1 (PLCζ1), which transcribes a key protein, has an important function in oocyte activation and embryo development because PLCζ1 can trigger a series of intracellular Ca 2+ oscillations in mammals. In this study, a novel splice variant in the testis tissues of adult and fetal Chinese Holstein bulls was characterized by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing analysis. The novel splice variant PLCζ1-sv1 was derived from the PLCζ1 complete transcript (PLCζ1-complete) by alternative splicing; the alternative splicing pattern exhibited alternative 5'-splice sites. The full-length transcript, PLCζ1-complete, is the main transcript found in fetal and adult cow testis tissue. Quantitative real-time PCR (qPCR) analysis demonstrated that the expression levels of the PLCζ1-complete transcript were significantly higher than those of the PLCζ1-sv1 splice variant in bovine testis tissues. PLCζ1 protein sequencing analysis showed that the amino acids at positions 453 to 457 were deleted in PLCζ1-sv1, thereby terminating transcription prematurely. In summary, this study provided information to elucidate the structure and function of the bovine PLCζ1 gene.

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Identification of a novel cis-element that regulates alternative splicing of Bcl-x pre-mRNA

Cited by 16 publications

References 37 publications

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8

SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene

Identification and characterization of a novel splice variant of the PLCζ1 gene in bull testis tissues

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