High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice

PloS One
Yu-Chia ChenChung-Yee Yuo

Abstract

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease caused by deletion or mutation of SMN1 gene. All SMA patients carry a nearly identical SMN2 gene, which produces low level of SMN protein due to mRNA exon 7 exclusion. Previously, we found that the testis of SMA mice (smn-/- SMN2) expresses high level of SMN2 full-length mRNA, indicating a testis-specific mechanism for SMN2 exon 7 inclusion. To elucidate the underlying mechanism, we established primary cultures of testis cells from SMA mice and analyzed them for SMN2 exon 7 splicing. We found that primary testis cells after a 2-hour culture still expressed high level of SMN2 full-length mRNA, but the level decreased after longer cultures. We then compared the protein levels of relevant splicing factors, and found that the level of Tra2-β1 also decreased during testis cell culture, correlated with SMN2 full-length mRNA downregulation. In addition, the testis of SMA mice expressed the highest level of Tra2-β1 among the many tissues examined. Furthermore, overexpression of Tra2-β1, but not ASF/SF2, increased SMN2 minigene exon 7 inclusion in primary testis cells and spinal cord neurons, whereas knockdown of Tra2-β1 decreased SMN2 exon 7 inclusion in primary testis...Continue Reading

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Citations

Jun 20, 2019·RNA Biology·Přemysl SoučekTomáš Freiberger
Jun 17, 2020·Expert Opinion on Therapeutic Targets·Ravindra N SinghNatalia N Singh

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Methods Mentioned

BETA
SMA
mechanical dissociation
Transfection
PCR
electrophoresis
X-ray
immunoprecipitations

Software Mentioned

LabWorks Image Acquisition and Analysis
Excel
LabWorks Image Analysis

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