The Biochemical Characterization of LINC00298; a Genetic Risk Factor for the Development of Alzheimer’s Disease
Rachel A Hellmann Whitaker- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Long non‐coding RNAs (lncRNAs) are ubiquitous throughout the human system, yet many of their biological functions remain unknown. LINC00298 RNA, a long intergenic non‐coding RNA (lincRNA), is known to be a genetic risk factor for the development of Alzheimer’s disease, but until now, it had not been biochemically characterized.
Method
Computational Modeling was used to develop secondary and tertiary structures of LINC00298 RNA. Liquid Chromatography (LC) and Mass Spectrometry (MS) (LC/MS) was used to identify the protein binding partners of LINC00298 RNA.
Result
Structural analysis of LINC00298 RNA indicated it is mostly comprised of stem‐loop secondary structural motifs, with an elongated tertiary structure that is dynamic, making it an ideal binding partner for numerous cellular proteins. Biological analysis of LINC0028 RNA indicated that it has 24 protein binding partners, which include: Histone H1.4, Histone H2AX, Histone H4, Pyruvate kinase, Alpha‐enolase, 40S Ribosomal proteins SA, S18, and S3, 60S Ribosomal proteins L31, L13, L13a, 60S acidic ribosomal protein P0 and P2, Prohibitin 1, ATP Synthase subunit alpha and subunit e, Heat Shock Protein HSP 90‐beta, Heterogeneous Nuclear Ribonucleoprotein A/B, Heterogeneous Nuclear Ribonucleoprotein U, Cofilin‐1 Elongation factor 2, Eukaryotic Initiation Factor 4A‐I, Dihydropyrimidinase‐related protein 2, and ADP/ATP Translocase 2.
Conclusion
Through analysis of these 24 protein binding partners, it was concluded that LINC00298 RNA may play significant roles in protein translation, as well as neuronal development, proliferation, and cellular organization. Furthermore, analysis of LINC00298 RNA’s interactome, indicated that LINC00298 RNA has dual localization in the nucleus and the cytosol. This biochemical characterization of LINC00298 RNA highlights the essential role it plays in many biological processes and the important need for continued research on LINC00298 RNA’s pathogenic role in the development of Alzheimer’s disease.