The MIR-NAT MAPT-AS1 does not regulate Tau expression in human neurons

Abstract

The MAPT gene encodes Tau protein, a member of the large family of microtubule-associated proteins. Tau forms large insoluble aggregates that are toxic to neurons in several neurological disorders and neurofibrillary Tau tangles represent a key pathological hallmark of Alzheimers disease (AD) and other tauopathies1,2. Several Tau-lowering strategies are being investigated as a potential treatment for AD but the mechanisms that regulate Tau expression at the transcriptional or translational level are not well understood3,4. Recently, Simone et al.5 reported the discovery of a new type of natural antisense transcripts called MIR-NATs (referring to Mammalian-wide Interspersed Repeats - Natural Antisense Transcripts). Simone and colleagues used MAPT-AS1, a MIR-NAT associated to the MAPT gene as an archetype of this new class of long non-coding RNAs. According to Simone et al., MAPT-AS1 represses Tau translation by competing for ribosomal RNA. We investigated the potential functions of MAPT-AS1 in neurons using the same gain- and loss-of-function experiments as described in the original report and expanded our analysis with complementary approaches. Our data do not support a role for MAPT-AS1 in regulating Tau expression in human neurons and urge to cautiously interpret the data provided by Simone et al.5.