The mRNA transcription/processing factor Ssu72 is a potential tyrosine phosphatase.
Ssu72 is an essential and highly conserved protein involved in mRNA transcription and 3'-end processing. The biochemical function of Ssu72 was so far unknown. We report here evidence that Ssu72 is a phosphatase that resembles protein tyrosine phosphatases (PTPases). First, recombinant Ssu72 cleaves the phosphotyrosine analogue p-nitrophenylphosphate, and this catalytic activity is impaired by PTPase-inhibiting agents. Second, the Ssu72 sequence contains the CX(5)R signature motif of PTPases; mutation of the catalytic cysteine in this motif abolishes Ssu72 activity in vitro and has been shown to confer lethality in vivo. Third, secondary structure prediction and site-directed mutagenesis predict that Ssu72 adopts the fold of PTPases of the low molecular weight family. Distinguishing features, such as a short "aspartate loop" at the active site, suggest however that Ssu72 is the founding member of a new phosphatase subfamily. The novel Ssu72 activity may regulate coupling events during mRNA biogenesis.
Meinhart
Anton
A
Institute of Biochemistry, Gene Center, University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Silberzahn
Tobias
T
Cramer
Patrick
P
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D002470:Cell Survival; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors
D002352:Carrier Proteins; D012333:RNA, Messenger; C416934:SSU72 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases