Figure 8.

Role of the EJC, Srp54, and ci RNA production in Hh signal transduction. In the absence of Hh, full-length Ci-155 protein is largely inactive and processed slowly, with the participation of PKA and Cos2, into active Ci-75 repressor. Hh signal transduction via activation of Smo leads to inhibition of Ci-155 processing, leading to a loss of Ci-75 repressor and a greater accumulation of Ci-155 primary translation product. Hh also promotes activation of Ci-155 via Fu kinase and in opposition to Su(fu). Activated Ci-155 is subject to Cul3-mediated degradation (data not shown). The role of Ci-155 levels in contributing to Hh target gene activation is not well-studied. Here, we have found that reduced rates of Ci-155 production due to reduced ci gene dose, genetic removal of ci intronic sequences, or reduced production of the major ci RNA (ci-A) through inhibition of core nuclear EJC factors or Srp54, reduce Hh pathway activity under conditions of submaximal activation (by Hh in the absence of Fu kinase, by synthetic Fu activation, or by loss of PKA or Cos2). Loss of Su(fu), like reduced Ci-155 production, only affects Hh pathway activity under an overlapping set of conditions for submaximal pathway activation, illustrating the potential for partial redundancy in regulating Ci-155 levels and Ci-155 activity. The minor ci-B RNA is increased in the absence of Mago and encodes a protein with normally regulated activator function but appears not to be processed to a functional repressor. EJC, exon junction complex; Fu, Fused; Hh, Hedgehog; PKA, Protein kinase A; Smo, Smoothened; Su(fu), Suppressor of fused.