Department of biochemistry and Molecular biology
Baby Tholanikunnel, PhD
Postdoctoral Fellow, Stony Brook University, Stony Brook, New York
Ph.D., Poona University, India
Office: (BSB-535B) 843-792-8503
My research is focused on RNA-binding proteins that regulate translation and localization of G protein-coupled receptor (GPCR) mRNA. We identified a novel regulatory pathway involving RNA-binding proteins in the synthesis and transport of GPCRs to the plasma membrane. This pathway, involves translational silencing and localization of mRNA to the cortical ER region of the cells. Our results suggest that cortical ER localized micro-domains within a particular cell surface can regulate complex signaling events including receptor mRNA localization, translational derepression, post-translational modification and delivery of mature receptors to the plasma membrane. Since GPCRs constitute the largest drug targets, identification of RNA-binding proteins with important roles in receptor trafficking provides an opportunity to design new drugs that target RNA regulatory proteins.
We use a variety of techniques in biochemistry, molecular biology and cell biology including RNA-affinity method to purify RNA-binding proteins, RNA electrophoretic mobility shift assays, fluorescent in situ hybridization (FISH) analysis coupled with immunofluorescence staining and confocal microscopy, polysome profile analysis to study mRNA translation, in vitro transcription and RNase protection assays, expression and purification of recombinant RNA-binding proteins and shRNA-mediated knockdown of mRNAs etc.
Recent Publications | Additional Publications
Joseph K, Spicer EK, and Tholanikunnel BG. (2013) Regulatory mechanism of G-protein-coupled receptor trafficking to the plasma membrane: a role for mRNA localization. Methods Enzymol 521:131-150. PMID: 23351737. Corresponding author.
Joseph K, Tholanikunnel BG, and Bygum A, Ghebrehiwet B, Kaplan AP. (2013) Factor XII-independent activation of the bradykinin-forming cascade: implications for the pathogenesis of hereditary angioedema types I and II. J Allergy Clin Immunol 132:470-475. PMID: 23672780.
Subramaniam K, Kandasamy K, Joseph K, Spicer EK, and Tholanikunnel BG. (2011) The 3’-untranslated region length and AU-rich RNA location modulate RNA-protein interaction and translational control of β2-AR mRNA. Mol Cell Biochem 352:125-41. PMID: 21369731. Corresponding author.
Clarke CJ, Mediwala K, Jenkins RW, Sutton, CA, Tholanikunnel BG, and Hannun YA. (2011) Neutral sphingomyelinase-2 mediates growth arrest by retinoic acid through modulation of ribosomal S6 kinase. J Biol Chem 286:21565-21576. PMID: 21536668.
Tholanikunnel BG, Joseph K, Kandasamy K, Baldys A, Raymond JR, Mcdermott P, Luttrell LM, and Fernandes DJ. (2010) Novel mechanisms in the regulation of G protein-coupled receptor trafficking to the plasma membrane. J Biol Chem 285:33816-33825. PMID: 20739277. Corresponding author.
Cowart LA, Gandy JL, Tholanikunnel BG, and Hannun YA. (2010) Sphingilipids mediate formation of mRNA processing bodies during the heat stress response of Saccharomyces Cervisiae. Biochem J 431:31-8. PMID: 20629639.
Ishimaru D, Ramalingam S, Sengupta TK, Bandyopadhyay S, Dellis S, Tholanikunnel BG, Fernandes DJ, and Spicer EK. (2009) Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells. Mol Cancer Res 7:1354-1366. PMID: 19671677.
Joseph K, Tholanikunnel BG, Kaplan AP. (2009) Factor XII-independent cleavage of high molecular weight kininogen by prekallikrein and inhibition by C1 inhibitor. J Allergy Clin Immunol 124:143-149. PMID: 19342086.
Kandasamy K, Joseph K, Subramaniam K, Raymond JR, and Tholanikunnel BG. (2005) Translational control of β2-adrenergic receptor mRNA by T-cell-restricted intracellular antigen-related protein. J Biol Chem 280:1931-43. PMID: 15536087. Corresponding author.
Subramaniam K, Chen K, Joseph K, Raymond JR, Tholanikunnel BG. (2004) The 3'-untranslated region of the β2-adrenergic receptor mRNA regulates receptor synthesis. J Biol Chem 279:27108-15. PMID: 15107422. Corresponding author.
Garnovskaya MN, Mukhin YV, Vlasova T, Grewal JS, Ullian ME, Tholanikunnel BG, and Raymond JR. (2004) Mitogen-induced rapid phosphorylation of serine 795 of the retinoblastoma gene product in vascular smooth muscle cells involves ERK activation. J Biol Chem 279:24899-905. PMID:15069084.
Joseph K, Tholanikunnel BG, and Kaplan AP. (2002) Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of Factor XII. Proc Natl Acad Sci USA 99:896-900. PMID: 11792853.
Tholanikunnel BG, Raymond JR, Malbon CC. (1999) Analysis of the AU-rich elements in the 3’-untranslated region of β2-adrenergic receptor mRNA by mutagenesis and identification of the homologous AU-rich region from different species. Biochemistry 38:15564-72. PMID:10569940. Corresponding author.
Tholanikunnel BG and Malbon CC. (1999) The analysis of post-transcriptional regulation of the expression of G-protein-linked receptors. In: Regulation of G-Protein-Coupled Receptor Function and Expression (JL Benovic, Ed) Wiley-Liss, 273-92.
Tholanikunnel BG and Malbon CC. (1997) A 20-nucleotide A+U-rich element of beta2-adrenergic receptor (beta2AR) mRNA mediates binding to beta2AR-binding proteins and is obligate for agonist-induced destabilization of receptor mRNA. J Biol Chem 273:11471-79. PMID: 9111060. Corresponding author.