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A novel species-specific RNA related to alternatively spliced amyloid precursor protein mRNAs
J S Jacobsen1, H A Muenkel, A J Blume
1Central Nervous System Biological Research Department, American Cyanamid Company, Pearl River, NY 10965.
Abstract:
Using an S1 nuclease protection assay, we have identified a novel "variant" Amyloid Precursor Protein (APP) RNA in human brain which is 3-6-fold more abundant than APP-770, but less abundant than APP-751 or APP-695. This variant, referred to as amyloid precursor-related protein 365 (APRP-365), is not detected in mouse and rat brain RNAs. A 1.6 kilo-basepair cDNA clone corresponding to this variant APP RNA predicts the existence of a 365 amino acid protein that is similar to the amino-terminal end of APP-770 but lacks the beta-amyloid peptide and any hydrophobic transmembrane spanning domains. In a modified polymerase chain reaction (PCR), we used amplification of reverse transcribed mRNA to confirm and extend our S1 observations. Together, the features of APRP-365 suggest that the human variant is a soluble protein containing a Kunitz protease inhibitor domain.
Insights
Researchers discovered a novel human variant Amyloid Precursor Protein (APP) RNA, termed amyloid precursor-related protein 365 (APRP-365), in the brain. This soluble protein variant lacks beta-amyloid peptides and transmembrane domains.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Amyloid Precursor Protein (APP) plays a crucial role in neurological functions.
- Previous research has identified various APP isoforms with differing functions.
- Understanding APP variants is key to deciphering complex brain processes.
Purpose of the Study:
- To identify and characterize novel Amyloid Precursor Protein (APP) RNA variants in the human brain.
- To determine the abundance and structural features of the newly identified variant.
- To investigate the potential function and localization of the variant protein.
Main Methods:
- S1 nuclease protection assay to detect and quantify RNA species.
- Reverse transcription followed by modified polymerase chain reaction (PCR) for confirmation.
- cDNA cloning and sequencing to predict protein structure.
Main Results:
- Identification of a novel human-specific APP variant RNA, designated amyloid precursor-related protein 365 (APRP-365).
- APRP-365 is 3-6 times more abundant than APP-770 in human brain RNA but not detected in rodent brains.
- The APRP-365 RNA encodes a 365 amino acid protein lacking beta-amyloid and transmembrane domains, suggesting a soluble nature.
- APRP-365 contains a Kunitz protease inhibitor domain.
Conclusions:
- APRP-365 represents a unique, soluble human-specific APP variant.
- The presence of a Kunitz protease inhibitor domain suggests a role in regulating protease activity.
- Further research is warranted to elucidate the precise physiological function of APRP-365 in the human brain.