DETERMINANTS OF SPECIFICITY IN PROTEIN-RNA INTERACTIONS

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This project is directed at the elucidation of mechanisms of RNA recognition by a family of RNA-binding proteins (RRM family) which have a common sequence motif. Novel members of the RRM family will be isolated using degenerate nucleic acid probing and antibody reactivity. Molecular genetic and biophysical methods will be used to elucidate amino acid determinants involved in RNA binding specificity by RRM family members which function in transcription (La and Ro) and RNA processing (U1 and U2 snRNP proteins). One aim will focus on a novel neuron- specific RRM protein, termed Hel-N1, which we have found can affect cell proliferation and differentiation when expressed in cultured cells. Our data indicate that Hel-N1 can bind to RNA "instability sequences" in the noncoding regions of oncoprotein and lymphokine messages, including c- myc, c-fos and GM-CSF. We propose to study the role of Hel-N1 and other RNA binding proteins in RNA stability, growth control and cellular transformation. Therefore, these studies will address fundamental mechanisms of RNA recognition and binding which function at many levels of nucleic acid metabolism and which regulate nucleic acid-protein interactions.