In mammalian oocytes, cyclic AMP-dependent protein kinase (PKA) is responsible 
for maintaining meiotic arrest. We examined the role of the predominant 
regulatory subunit, RIalpha in regulating PKA activity during mouse oocyte 
maturation by knocking down the protein levels using an RNA interference 
approach. In oocytes in which RIalpha protein was reduced to non-detectable 
levels, compensatory decreases were also observed in the RIIalpha and catalytic 
(Calpha) subunit levels. These oocytes resumed meiosis, despite culture under 
conditions that maintain elevated intracellular cAMP levels, suggesting that the 
remaining Calpha was not sufficient to maintain meiotic arrest. The resulting 
eggs, however, displayed meiotic spindle abnormalities and abnormal cleavage 
planes leading to extrusion of large polar bodies. These results demonstrate 
that RIalpha is required for regulating PKA activity in maturing oocytes and 
that compensatory upregulation of RII does not occur. Furthermore, we implicate 
PKA as a modulator of spindle morphology and function during meiosis.