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

Policarpo, R.; Wolfs, L.; Martinez-Montero, S.; Vandermeulen, L.; Royaux, I.; Van Peer, G.; Mestdagh, P.; Sierksma, A.; De Strooper, B.; d'Ydewalle, C.

doi:10.1101/2023.01.27.525631

bioRxiv · 10.1101/2023.01.27.525631

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

Policarpo, R.·Wolfs, L.·Martinez-Montero, S.·Vandermeulen, L.·Royaux, I.·Van Peer, G.·Mestdagh, P.·Sierksma, A.·De Strooper, B.·d'Ydewalle, C.

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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.

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Policarpo, R., Wolfs, L., Martinez-Montero, S., Vandermeulen, L., Royaux, I., Van Peer, G., Mestdagh, P., Sierksma, A., De Strooper, B., d'Ydewalle, C.. 2023-01-27. The MIR-NAT MAPT-AS1 does not regulate Tau expression in human neurons. https://doi.org/10.1101/2023.01.27.525631

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