In Silico characterization of phosphorylase kinase: Evidence for an alternate intronic polyadenylation site in PHKG1

• Published in: Molecular genetics and metabolism Vol. 92; no. 3; pp. 234 - 242
• Main Authors: Winchester, Joni S., Rouchka, Eric C., Rowland, Naomi S., Rice, Nancy A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2007
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Composite exon; Computational Biology; Humans; Introns - genetics; Molecular Sequence Data; PHKG1; Phosphorylase kinase; Phosphorylase Kinase - deficiency; Phosphorylase Kinase - genetics; Polyadenylation; RNA, Messenger; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Tissue Distribution; Alternative splicing; PHKG1; Phosphorylase kinase; Composite exon; Polyadenylation
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2007.06.015

Phosphorylase kinase (PhK), the key enzyme that regulates glycogenolysis, has traditionally been thought to be expressed predominantly in muscle and liver. In this study, we show by two different database searches (Expressed Sequence Tag and UniGene) that PhK gene expression occurs in at least 28–36 different tissues, and that the genes encoding the α, β, and γ subunits of PhK undergo extensive transcriptional processing. In particular, we have identified exon 6 of PHKG1 as a 3′ composite terminal exon due to the presence of a weak polyadenylation and cleavage site in intron 6. We have verified biochemically that transcriptional processing of PHKG1 does occur
in vivo; mRNA corresponding to the alternate variant is expressed in skeletal muscle, brain, heart, and tongue.
In silico translation of this mRNA yields a PhK γ subunit that contains the first 181 residues of the protein, followed by an additional 21 amino acids. The implication of this alternate processing is discussed within the context of γ catalysis and regulation.