Photo of Ravinder Singh

Ravinder Singh

Associate Professor
303.492.8886
Ravinder.Singh@Colorado.EDU
Gold room A245C
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ORCID

Education

Ph.D., Baylor College of Medicine, 1990

Biography

Research Interests:
RNA-protein interactions in gene regulation; pre-mRNA splicing and sex determination; computational analysis of splicing regulation.

Research Profile:
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.

Selected Publications

A conditional role of U2AF in splicing of introns with unconventional polypyrimidine tracts.
Sridharan, V and Singh, R Mol Cell Biol, 27(20):7334-44. 2007

Genome-wide identification of alternatively spliced mRNA targets of specific RNA-binding proteins.
Robida, MD, Rahn, A, and Singh, R PLoS ONE, 2(6):e520. 2007

Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline.
Gawande, B, Robida, MD, Rahn, A, and Singh, R EMBO J, 25(6):1263-72. 2006

Fast-Find: a novel computational approach to analyzing combinatorial motifs.
Hamady, M, Peden, E, Knight, R, and Singh, R BMC Bioinformatics, 7:1. 2006

Building specificity with nonspecific RNA-binding proteins.
Singh, R and Valcarcel, J Nat Struct Mol Biol, 12(8):645-53. 2005

The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro.
Banerjee, H, Rahn, A, Gawande, B, Guth, S, Valcarcel, J, and Singh, R RNA, 10(2):240-53. 2004

Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in the male germline.
Robida, MD and Singh, R EMBO J, 22(12):2924-33. 2003

Sex lethal and U2 small nuclear ribonucleoprotein auxiliary factor (U2AF65) recognize polypyrimidine tracts using multiple modes of binding.
Banerjee, H, Rahn, A, Davis, W, and Singh, R RNA, 9(1):88-99. 2003

RNA-protein interactions that regulate pre-mRNA splicing.
Singh, R Gene Expr, 10(1-2):79-92. 2002

Differential recognition of the polypyrimidine-tract by the general splicing factor U2AF65 and the splicing repressor sex-lethal.
Singh, R, Banerjee, H, and Green, MR RNA, 6(6):901-11. 2000