PPP1R8 is an inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA. Instead, it may target PP-1 to RNA-associated substrates . PPP1R8 is also involved in pre-mRNA splicing, binds DNA, and might act as a transcriptional repressor . It seems to be required for cell proliferation .
The PPP1R8 gene, through alternative splicing, encodes three different isoforms . Two of these isoforms are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA . The third isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli . This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA .
PPP1R8 is involved in several critical cellular processes, including:
Mutations or dysregulation of PPP1R8 have been associated with various diseases. For instance, it is linked to Seckel Syndrome 5, a disorder characterized by growth retardation and microcephaly . Understanding the function and regulation of PPP1R8 can provide insights into the mechanisms underlying these conditions and potentially lead to therapeutic interventions.