| First Author | Jiang L | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 20 | Pages | 4209-4227.e12 |
| PubMed ID | 34453888 | Mgi Jnum | J:315841 |
| Mgi Id | MGI:6831130 | Doi | 10.1016/j.molcel.2021.07.038 |
| Citation | Jiang L, et al. (2021) Interaction of tau with HNRNPA2B1 and N(6)-methyladenosine RNA mediates the progression of tauopathy. Mol Cell 81(20):4209-4227.e12 |
| abstractText | The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N(6)-methyladenosine (m(6)A) modified RNA transcripts. Knockdown of HNRNPA2B1 prevents oTau or oTau-c from associating with m(6)A or from reducing protein synthesis and reduces oTau-induced neurodegeneration. Levels of m(6)A and the m(6)A-oTau-HNRNPA2B1 complex are increased up to 5-fold in the brains of Alzheimer subjects and P301S tau mice. These results reveal a complex containing oTau, HNRNPA2B1, and m(6)A that contributes to the integrated stress response of oTau. |
