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Increased Alu RNA processing in Alzheimer brains is linked to gene expression changes


ABSTRACT: Despite significant steps in our understanding of Alzheimer's Disease (AD), many of the molecular processes underlying its pathogenesis remain largely unknown. Here we focus on the role of non-coding RNAs produced by Small Interspersed Nuclear Elements (SINEs). RNAs from SINE B2 repeats in mouse and SINE Alu repeats in human, long regarded as "junk" DNA, control gene expression by binding RNA polymerase II and suppressing transcription. They also possess self-cleaving activity that is accelerated through their interaction with certain proteins disabling this suppression. Here we show that similar to mouse SINE RNAs, human Alu RNAs, are processed, and the processing rate is increased in brains of AD patients. This increased processing correlates with the activation of genes upregulated in AD patients, while increased intact Alu RNA levels correlate with downregulated gene expression in AD. In vitro assays show that processing of Alu RNAs is accelerated by HSF1. Overall, our data show that RNAs from SINE elements in the human brain show a similar pattern of deregulation during amyloid beta pathology as in mouse.

SUBMITTER: Yubo Cheng 

PROVIDER: S-SCDT-EMBOR-2020-52255V1 | biostudies-other |

REPOSITORIES: biostudies-other

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