172286-77-0

PK4C9 is a splice modulator of survival of motor neuron gene SMN2 th at increases production of full-length SMN protein. Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency in SMN protein resulting from loss of expression of the SMN1 gene. The related SMN2 gene can compensatebut polymorphism in SMN2 often results in altered splicing and exclusion of exon 7which is required for a full-length SMN transcript. PK4C9 binds to pentaloop conformations of the stem-loop RNA structure TSL2a cis-regulatory element for E7 inclusionand promotes a shift to triloop conformations th at display enhanced E7 splicing. In SMA cellsPK4C9 increased E7 inclusion by 40% accompanied by a 1.5-fold increase in SMN proteina level shown to reverse SMA phenotypes in mice models.