Section: Research

Ravindra Singh, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program
   Molecular Genetics and Microbiology
   Program in Neuroscience

Use of evolutionary selection to understand alternative splicing and the protein function

A vast majority of cellular proteins and protein complexes interact with nucleic acids (DNA and RNA) to regulate biochemical processes vital for cell survival. Evolutionary selection or SELEX (Systematic Evolution of Ligands through EXponential enrichment) has been at the forefront of identifying critical features of nucleic acid-protein interactions. In recent years, the technique of SELEX has been applied to produce high affinity ligands that could also be used for therapeutic and diagnostic applications. My laboratory is involved in developing powerful SELEX (in vivo and in vitro) protocols to analyze sequences that are critical for alternative splicing and protein function. As a model system, we have chosen Survival of Motor Neuron (SMN) Gene, which produces a multifunctional protein. Two SMN genes (SMN1 and SMN2) that code for identical proteins are located as inverted repeat on chromosome 5 (location 5q11-q13) of human genome. Due to a translationally silent cytidine-to-thymidine mutation (C6T substitution) in exon 7, most spliced products of SMN2 gene lack exon 7. This produces a truncated protein (SMND7), which has unknown biochemical function. The lack of full-length SMN protein leads to spinal muscular atrophy (SMA), where as the loss of SMND7 is associated with a number of diseases including amyotrophic lateral sclerosis (ALS), lower motor neuron disease (LMND) and multifocal motor neuropathy (MMN). Both proteins (SMN and SMND7) bind to nucleic acids, however the role of nucleic acid binding property has been poorly understood. Through a variety of SELEX techniques, my laboratory is engaged in identifying novel SMN-nucleic acid interactions.

Office: Research 326
Phone: 508-856-1333
Fax: 508-856-6797
E-mail: Ravindra.Singh.Forward@umassmed.edu
Keywords: RNA Biology, Gene Therapy, RNA Splicing, Gene Expression, Gene Regulation

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