Markers of mRNA stabilization and degradation, and RNAi within astrocytoma GW bodies.
GW bodies (GWBs) are unique cytoplasmic structures that contain the mRNA binding protein GW182 and other proteins involved in mRNA processing pathways. The rationale for this study arose from clinical studies indicating that 33% of patients with GWB autoantibodies have a motor/sensory neuropathy and/or ataxia. The novelty of this study is the identification of GWBs in astrocytes and astrocytoma cells within cell bodies and cytoplasmic projections. Astrocytoma GWBs exhibit complex heterogeneity with combinations of LSm4 and XRN1 as well as Ago2 and Dicer, key proteins involved in mRNA degradation and RNA interference, respectively. GWB subsets contained the mRNA transport and stabilization proteins SYNCRIP, hnRNPA1, and FMRP, not previously described as part of the GWB complex. Immunoprecipitation of astrocytoma GWBs suggested that Dicer, hDcp, LSm4, XRN1, SYNCRIP, and FMRP form a multiprotein complex. GWBs are likely involved in a number of regulatory mRNA pathways in astrocytes and astrocytoma cells.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada.
Joanna J
JJ
Moser
Theophany
T
Eystathioy
Edward K L
EK
Chan
Marvin J
MJ
Fritzler
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics* / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism
D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins; D004722:Endoribonucleases; D005095:Exoribonucleases; D051860:Fragile X Messenger Ribonucleoprotein 1; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D017411:Ribonucleoproteins, Small Nuclear; C497684:Fmr1 protein, mouse; C403621:Lsm4 protein, mouse; C486049:Syncrip protein, mouse; C107008:Xrn1 protein, mouse; C509781:Dicer1 protein, mouse