An antisense-long-noncoding-RNA modulates p75^NTR expression levels during neuronal polarization

Proper polarization of newly generated neurons is a critical process for neural network formation and brain development. The pan-neurotrophin p75^NTR receptor plays a key role in this process localizing asymmetrically in one of the differentiating neurites and specifying its axonal identity in response to neurotrophins. During axonal specification, p75^NTR levels are transiently modulated, yet the molecular mechanisms underlying this process are not known. Here, we identified a previously uncharacterized natural antisense transcript, AS-p75, encoded within the p75NGFR mouse gene. Using an in vitro model of polarizing murine neurons, we found that AS-p75 and p75^NTR display divergent expression profiles and that p75^NTR expression levels increase upon competition or depletion of AS-p75, indicating that AS-p75 is a negative regulator of p75^NTR expression. Depletion of AS-p75 also results in altered p75^NTR subcellular distribution and affects the polarization process. Overall, our data uncovered AS-p75 as a modulator of p75^NTR expression, offering new insights into the regulation of this neurotrophin receptor during in vitro neuronal polarization.