Regulation of thyroid hormone receptor alpha2 RNA binding and subcellular localization by phosphorylation.
Thyroid hormone receptor alpha2 (TRalpha2) is an alternative splice product of the TRalpha primary transcript whose unique carboxyl terminus does not bind T3 or activate transcription. The physiological function of TRalpha2 is unknown. We have found that TRalpha2 is a single stranded RNA binding protein and that the RNA binding domain localizes to a 41 amino acid region immediately distal to the second zinc finger. TRalpha2 contains a single protein kinase CK2 phosphorylation site in its amino terminus and potentially nine CK2 sites in its unique carboxyl terminus. In vitro CK2 treatment of TRalpha2 eliminated its RNA binding. Mutational analysis indicated that phosphorylations at the N- and C-terminal sites both contribute to this inhibitory effect. Cellular localization studies demonstrated that phosphorylated TRalpha2 is primarily cytoplasmic, whereas unphosphorylated TRalpha2 is primarily nuclear. Since RNA binding is a property of unphosphorylated TRalpha2, the TRalpha2-RNA interaction likely represents a nuclear function of TRalpha2.
Xu
Bin
B
Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, 5560 MSRB II, 1150 West Medical Center Dr., Ann Arbor, 48109-0678, USA.
Koenig
Ronald J
RJ
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D047390:Casein Kinase II / Q000032:analysis / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000502:physiology; D003593:Cytoplasm / Q000737:chemistry* / Q000502:physiology; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D009154:Mutation; D010766:Phosphorylation; D012313:RNA / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000502:physiology; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D051381:Rats; D037021:Thyroid Hormone Receptors alpha / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics
D000596:Amino Acids; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D037021:Thyroid Hormone Receptors alpha; C405423:steroid receptor RNA activator; D012313:RNA; D047390:Casein Kinase II