Beta Amyloid Peptide: Research Paper : Evidence of A Negative Feedback Network Between TDP-43 and miRNAs Dependent on TDP-43 Nuclear Localization

Evidence of A Negative Feedback Network Between TDP-43 and miRNAs Dependent on TDP-43 Nuclear Localization

Abstract

TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein that is integral to RNA processing. Among these functions is a critical role in microRNA (miRNA) biogenesis through interactions with the DROSHA and DICER complexes. It has been previously shown that there is a general reduction in miRNA levels within the spinal cord and spinal motor neurons of amyotrophic lateral sclerosis (ALS) patients. In addition, the most common pathological feature of ALS is re-distribution of TDP-43 from the nucleus to the cytoplasm where it forms cytoplasmic inclusions. Among miRNAs dysregulated in ALS, several are known to regulate TDP-43 expression. In this study, we demonstrate that TDP-43 is in a regulatory negative feedback network with miR-181c-5p and miR-27b-3p that is dependent on its nuclear localization within HEK293T cells. Further, we show that cellular stress which induces a redistribution of TDP-43 from the nucleus to the cytoplasm correlates with the reduced production of miR-27b-3p and miR-181c-5p. This suggests that reduced nuclear TDP-43 disrupts a negative feedback network between itself and miRNAs. These findings provide a further understanding of altered miRNA biogenesis as a key pathogenic process in ALS.

Keywords: ALS; TDP-43; cell stress; miR-181c; miR-27b; microRNAs.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33137311/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.