Identification of an mRNA-decapping regulator implicated in X-linked mental retardation.
Two major decapping enzymes are involved in the decay of eukaryotic mRNA, Dcp2 and DcpS. Despite the detection of robust DcpS decapping activity in cell extract, minimal to no decapping is detected from human Dcp2 (hDcp2) in extract. We now demonstrate that one reason for the lack of detectable hDcp2 activity in extract is due to the presence of inhibitory trans factor(s). Furthermore, we demonstrate that a previously identified testis-specific protein of unknown function implicated in nonspecific X-linked mental retardation, VCX-A, can function as an inhibitor of hDcp2 decapping in vitro and in cells. VCX-A is a noncanonical cap-binding protein that binds to capped RNA but not cap structure lacking an RNA. Its cap association is enhanced by hDcp2 to further augment the ability of VCX-A to inhibit decapping. Our data demonstrate that VCX-A can regulate mRNA stability and that it is an example of a tissue-specific decapping regulator.
Jiao
Xinfu
X
Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854.
Wang
Zuoren
Z
Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854.
Kiledjian
Megerditch
M
Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854. Electronic address: kiledjian@biology.rutgers.edu.
D002460:Cell Line; D004722:Endoribonucleases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D038901:X-Linked Intellectual Disability / Q000378:metabolism*; D009687:Nuclear Proteins / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
D009687:Nuclear Proteins; D012333:RNA, Messenger; C404411:VCX protein, human; D004722:Endoribonucleases; C467723:DCP2 protein, human