Protein phosphatase 2A family members (PP2A and PP6) associate with U1 snRNP and the spliceosome during pre-mRNA splicing.
Protein phosphorylation and dephosphorylation are both important for multiple steps in the splicing pathway. Members of the PP1 and PP2A subfamilies of phospho-serine/threonine phosphatases play essential but redundant roles in the second step of the splicing reaction. PP6, a member of the PP2A subfamily, is the mammalian homolog of yeast Sit4p and ppe1, which are involved in cell cycle regulation; however, the involvement of PP6 in the splicing pathway remains unclear. Here we show that PP2A family members physically associate with the spliceosome throughout the splicing reaction. PP2A holoenzyme and PP6 were found stably associated with U1 snRNP. Together our findings indicate that these phosphatases regulate splicing catalysis involving U1 snRNP and suggest an important evolutionary conserved role of PP2A family phosphatases in pre-mRNA splicing.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Electronic address: malekkam@mail.med.upenn.edu.
Malek
M
Kamoun
Mohammed
M
Filali
Michael V
MV
Murray
Sita
S
Awasthi
Brian E
BE
Wadzinski
D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism*; D060168:Thymocytes / Q000378:metabolism
D017412:Ribonucleoprotein, U1 Small Nuclear; D017413:Ribonucleoprotein, U2 Small Nuclear; C517189:PPP2CA protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C106079:protein phosphatase 6
PP2A; PP6; Phosphatase; Pre-mRNA splicing; snRNPs