DETERMINANTS OF SPECIFICITY IN PROTEIN-RNA INTERACTIONS

该项目旨在阐明RNA的作用机制， 被RNA结合蛋白家族（RRM家族）识别，这些蛋白具有 一个共同的序列基序 RRM家族的新成员将是 使用简并核酸探测和抗体反应性分离。 分子遗传学和生物物理学方法将用于阐明氨基酸 RRM家族参与RNA结合特异性的酸性决定簇 在转录（La和Ro）和RNA加工中起作用的成员 (U1和U2 snRNP蛋白）。 其中一个目标将集中在一个新的神经元上- 我们发现一种称为Hel-N1特异性RRM蛋白能够影响细胞 当在培养的细胞中表达时增殖和分化。 我们 数据表明，Hel-N1可以结合RNA“不稳定序列”， 癌蛋白和淋巴因子信息的非编码区，包括c- myc、c-fos和GM-CSF。 我们建议研究Hel-N1和其他 RNA结合蛋白在RNA稳定性、生长控制和细胞增殖中的作用 转型 因此，这些研究将解决基本的 RNA识别和结合机制在许多水平上发挥作用 调节核酸-蛋白质 交互.

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.