High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice.
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) e...
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doaj-51a1a0f5d40b47b495dea0a95e9126452020-11-25T01:45:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012072110.1371/journal.pone.0120721High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice.Yu-Chia ChenJan-Gowth ChangYuh-Jyh JongTing-Yuan LiuChung-Yee YuoSpinal 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 cells of SMA mice. Therefore, our results indicate that high expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. This study also suggests that the expression level of Tra2-β1 may be a modifying factor of SMA disease and a potential target for SMA treatment.http://europepmc.org/articles/PMC4363149?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-Chia Chen Jan-Gowth Chang Yuh-Jyh Jong Ting-Yuan Liu Chung-Yee Yuo |
spellingShingle |
Yu-Chia Chen Jan-Gowth Chang Yuh-Jyh Jong Ting-Yuan Liu Chung-Yee Yuo High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. PLoS ONE |
author_facet |
Yu-Chia Chen Jan-Gowth Chang Yuh-Jyh Jong Ting-Yuan Liu Chung-Yee Yuo |
author_sort |
Yu-Chia Chen |
title |
High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. |
title_short |
High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. |
title_full |
High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. |
title_fullStr |
High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. |
title_full_unstemmed |
High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. |
title_sort |
high expression level of tra2-β1 is responsible for increased smn2 exon 7 inclusion in the testis of sma mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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 cells of SMA mice. Therefore, our results indicate that high expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. This study also suggests that the expression level of Tra2-β1 may be a modifying factor of SMA disease and a potential target for SMA treatment. |
url |
http://europepmc.org/articles/PMC4363149?pdf=render |
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