Ravinder Singh - Associate Professor
Ph.D., Baylor College of Medicine, 1990
In eukaryotes, RNA-binding proteins regulate several aspects of developmental programs in metazoans. We study Drosophila sexual differentiation in a functional setting - in the context of somatic cells, male germ cells, and female germ cells. We use computational, biochemical, molecular, and genetic techniques to study post-transcriptional gene regulation, such as splicing, polyadenylation, and translation.
Sex determination is fundamental to all higher eukaryotes. Sex determination in Drosophila is the best understood example of splicing regulation. Alternative splicing provides an important source of molecular diversity. The Sex-lethal (SXL) protein acts as the master sex switch in D. melanogaster causing female development. Previous genetic studies suggest that Sxl regulates additional genes particularly in the female germline. Our recent findings are:
(1) The RNA Recognition Motifs (RRM1 and 2) of U2AF65 and SXL use a new mechanism for Py-tract recognition - multiple modes of binding - resulting in an ensemble of complexes.
(2) Our genome-wide computational search for additional targets of SXL has identified that SXL regulates a new target by a novel mechanism: sex-specific polyadenylation switching.
(3) The poly(A) switching provides a means for translation repression in the female germline.
(4) The Drosophila Polypyrimidine-tract-binding protein (PTB) functions specifically in the male germline.
(5) The conserved RRM3 domain of U2AF65 is dispensable for splicing in vitro.
Robida MD, Rahn A, Singh R, "Genome-wide identification of alternatively spliced mRNA targets of specific RNA-binding proteins" PLoS ONE 2 (2007): e520
Singh, R, Robida, M, Sina K, "Building Biological Complexity with Limited Genes" Current Genomics 7 (2006): 97-114
Gawande B, Robida MD, Rahn A, Singh R, "Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline." The EMBO journal 25 (2006): 1263-72
Zhang W, Li B, Singh R, Narendra U, Zhu L, Weiss MA, "Regulation of sexual dimorphism mutational and chemogenetic analysis of the doublesex DM domain" Molecular and cellular biology 26 (2006): 535-47
Hamady M, Peden E, Knight R, Singh R, "Fast-Find: A novel computational approach to analyzing combinatorial motifs" BMC Bioinformatics 7 (2006)
Singh R, Valcárcel J, "Building specificity with nonspecific RNA-binding proteins." Nature structural & molecular biology 12 (2005): 645-53
Banerjee H, Rahn A, Gawande B, Guth S, Valcarcel J, Singh R, "The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro." RNA (New York, N.Y.) 10 (2004): 240-53
Singh R, Nielsen AL, Johansen MG, Jørgensen AL, "Genetic polymorphism and sequence evolution of an alternatively spliced exon of the glial fibrillary acidic protein gene, GFAP" Genomics 82 (2003): 185-93
Robida MD, Singh R, "Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in the male germline." The EMBO journal 22 (2003): 2924-33
Banerjee H, Rahn A, Davis W, Singh R, "Sex lethal and U2 small nuclear ribonucleoprotein auxiliary factor (U2AF65) recognize polypyrimidine tracts using multiple modes of binding." RNA (New York, N.Y.) 9 (2003): 88-99
Singh R, "RNA-protein interactions that regulate pre-mRNA splicing." Gene expression 10 (2002): 79-92
Singh R, Banerjee H, Green MR, "Differential recognition of the polypyrimidine-tract by the general splicing factor U2AF65 and the splicing repressor sex-lethal." RNA (New York, N.Y.) 6 (2000): 901-11
Shivakrupa, Singh, Swarup, "Identification of a novel splice variant of C3G which shows tissue-specific expression" DNA and cell biology 18 (1999): 701-8
