NUCLEOLIN AND HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-C PROTEINS SPECIFICALLY INTERACT WITH THE 3'-UNTRANSLATED REGION OF AMYLOID PROTEIN-PRECURSOR MESSENGER-RNA

The central nervous system deposition by neurons and glia of beta A4 a myloid protein is an important contributing factor to the development of Alzheimer's disease. Amyloidogenic cells overexpress amyloid precur sor protein (APP) mRNAs suggesting a transcriptional or posttranscript ional defect may contribute to this process. We have previously shown that APP mRNAs display regulated stability which is dependent on a 29- base element within the 3'-untranslated region (UTR). This domain spec ifically interacted with several cytoplasmic RNA-binding proteins. We have purified these APP RNA-binding proteins from a human T-cell leuke mia and demonstrate that five cytoplasmic proteins of 70, 48, 47, 39, and 38 kDa form the previously observed APP RNA protein complexes. Ami no acid sequence analyses showed that the 70-, 48-, and 47-kDa protein s were fragments of nucleolin and that the 39- and 38-kDa proteins wer e heterogeneous nuclear ribonucleoprotein (hnRNP) C protein. Northwest ern and Western blot analyses of purified material further confirmed t hese data. Nucleolin protein is known to shuttle between the nucleus a nd cytoplasm but hnRNP C has not been reported within the cytoplasm. T his report of sequence specific, mRNA binding by nucleolin Emd hnRNP C suggests that these proteins participate in the post-transcriptional regulation of APP mRNA through 3'-UTR, site-specific interactions.