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

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 Alzheimer's disease (AD) and other 'tauopathies'. 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 understood. Recently, Simone et al. 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. ### Competing Interest Statement CdY is an employee of Janssen Pharmaceutica, pharmaceutical companies of Johnson & Johnson. In connection with such employment, CdY receives salary, benefits, and stock-based compensations including stock options, restricted stock and other stock-related grants. CdY and SMM hold patents covering methods to modify Tau expression. BDS is scientific founder of Augustine Therapeutics and Muna Therapeutics, two biotech companies that do not work on Tau.