| First Author | Koranda JL | Year | 2018 |
| Journal | Neuron | Volume | 99 |
| Issue | 2 | Pages | 283-292.e5 |
| PubMed ID | 30056831 | Mgi Jnum | J:269773 |
| Mgi Id | MGI:6269132 | Doi | 10.1016/j.neuron.2018.06.007 |
| Citation | Koranda JL, et al. (2018) Mettl14 Is Essential for Epitranscriptomic Regulation of Striatal Function and Learning. Neuron 99(2):283-292.e5 |
| abstractText | N(6)-methyladenosine (m(6)A) regulates mRNA metabolism and translation, serving as an important source of post-transcriptional regulation. To date, the functional consequences of m(6)A deficiency within the adult brain have not been determined. To achieve m(6)A deficiency, we deleted Mettl14, an essential component of the m(6)A methyltransferase complex, in two related yet discrete mouse neuronal populations: striatonigral and striatopallidal. Mettl14 deletion reduced striatal m(6)A levels without altering cell numbers or morphology. Transcriptome-wide profiling of m(6)A-modified mRNAs in Mettl14-deleted striatum revealed downregulation of similar striatal mRNAs encoding neuron- and synapse-specific proteins in both neuronal types, but striatonigral and striatopallidal identity genes were uniquely downregulated in each respective manipulation. Upregulated mRNA species encoded non-neuron-specific proteins. These changes increased neuronal excitability, reduced spike frequency adaptation, and profoundly impaired striatal-mediated behaviors. Using viral-mediated, neuron-specific striatal Mettl14 deletion in adult mice, we further confirmed the significance of m(6)A in maintaining normal striatal function in the adult mouse. |
