Interaction of Amyloid Beta with Mitochondrial RNAs

Abstract

AbstractBackgroundDespite mitochondrial RNA’s (mt‐RNA) polycistronic origin, research has shown that a number of post‐transcriptional mechanisms can control transcription. The amyloidogenic proteins such as prion and aSyn are known to bind RNA. However, the main peptide responsible for the pathogenesis of Alzheimer’s disease (AD), amyloid beta 1‐42 (Aβ1‐42), is not known to interact with RNA. It is well known that Aβ1‐42 is an alpha‐helix in monomer form. However, by attaching zinc, Aβ1‐42 achieves sheet folding. Aβ’s new conformation resembles zinc finger transcription factors. Furthermore, using randomly generated RNA molecules, it has been shown that the Aβ peptide domain that interacts with metals may also interact with RNA. As a result, Aβ has the potential to interact with mtRNAs, and this possible interaction may be linked to malfunctioning mitochondria in AD. Aβ1‐42, on the other hand, may affect the LRP130 protein, which is implicated in the mtRNA post‐transcriptional processes. In the current study, we seek to determine whether Aβ1‐42 may interact with mtRNA and whether Aβ1‐42 treatment affects LRP130’s ability to bind to mtRNA.MethodIn our study, the possible interaction of Aβ1‐42‐mtRNA and whether LRP130’s binding capacity to mtRNA was changed due to 0,1µM of Aβ1‐42 peptide treatment was investigated by RNA immunoprecipitation (RNA‐IP) and qRT‐PCR in differentiated LUHMES cells.ResultAβ – RNA IP experiment revealed that certain specific mtRNA binding signals were detected in untreated cells, albeit at a low level. Compared to untreated cells, the administration of Aβ1‐42 dramatically reduced LRP130’s affinity for mtRNAs.ConclusionAβ1‐42, the major peptide of AD, may be able to influence post‐transcriptional mitochondrial expression. When we consider the significance of RNA‐protein interactions in neurodegenerative processes, we determine that our research can offer a current strategy for AD biomarker research and the generation of therapeutic RNA aptamers. This study is supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (Project ID:219Z179).