@entity2057 ( @entity2057 ) is one of the most common inherited causes of pediatric mortality. @entity2057 is caused by deletions or mutations in the @entity11280 ( @entity11280 ) gene, which results in @entity1131 . @entity1 have a centromeric copy of the survival of motor neuron gene, @entity23247 , which is nearly identical to @entity11280 . However, @entity23247 cannot compensate for the loss of @entity11280 because @entity23247 has a single- @entity377 difference in exon 7, which negatively affects splicing of the exon. As a result, most mRNA produced from @entity23247 lacks exon 7. @entity23247 mRNA lacking exon 7 encodes a truncated protein with reduced functionality. Improving @entity23247 exon 7 inclusion is a goal of many @entity2057 therapeutic strategies. The identification of regulators of exon 7 inclusion may provide additional therapeutic targets or improve the design of existing strategies. Although a number of regulators of exon 7 inclusion have been identified, the function of most splicing proteins in exon 7 inclusion is unknown. Here, we test the role of SR proteins and hnRNP proteins in @entity23247 exon 7 inclusion. Knockdown and overexpression studies reveal that @entity19593 , @entity5313 , @entity25835 , @entity53149 , @entity68730 , @entity45464 , @entity47133 , @entity68731 , @entity24092 and @entity49864 can inhibit exon 7 inclusion. Depletion of two of the most potent inhibitors of exon 7 inclusion, @entity5313 or @entity25835 , in cell lines derived from @entity2057 @entity1 , increased @entity23247 exon 7 inclusion and SMN protein. Our results identify novel regulators of @entity23247 exon 7 inclusion, revealing potential targets for @entity2057 therapeutics.

Targeting SR Proteins Improves SMN Expression in XXXX Cells.

@entity1 :: ('9606', 'Species') :: ['patients', 'Humans'] @entity49864 :: ('3192', 'Gene') :: ['hnRNP U'] @entity23247 :: ('6607', 'Gene') :: ['SMN2'] @entity1131 :: ('MESH:D011488', 'Disease') :: ['SMN protein deficiency'] @entity53149 :: ('6429', 'Gene') :: ['SRSF4'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity68730 :: ('6430', 'Gene') :: ['SRSF5'] @entity24092 :: ('3178', 'Gene') :: ['hnRNPA1/B1'] @entity19593 :: ('6426', 'Gene') :: ['SRSF1'] @entity68731 :: ('9295', 'Gene') :: ['SRSF11'] @entity25835 :: ('6428', 'Gene') :: ['SRSF3'] @entity11280 :: ('6606', 'Gene') :: ['SMN1', 'survival of motor neuron 1'] @entity47133 :: ('6432', 'Gene') :: ['SRSF7'] @entity2057 :: ('MESH:D009133', 'Disease') :: ['Spinal muscular atrophy', 'SMA'] @entity5313 :: ('6427', 'Gene') :: ['SRSF2'] @entity45464 :: ('6431', 'Gene') :: ['SRSF6']
@entity2057 :: (MESH:D009133,Disease) :: ['Spinal Muscular Atrophy']
