Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz J, Peng J, Moore MJ, Yu G.
Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes.
J Biol Chem. 2011 Jan 14;286(2):1204-15.
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This paper by Gang Yu and colleagues describes a very interesting study to identify the set of RNAs that bind to TDP-43, a protein that has been implicated in a wide range of neurodegenerative diseases. The authors performed an unbiased screen of TDP-43 RNA targets and found over 4,000 RNAs that were bound to TDP-43. The TDP-43-binding RNAs had diverse physiological roles, primarily involving synaptic function, RNA metabolism, and neuronal development. Importantly, several RNAs involved in neurodegeneration were identified, including those for TDP-43 itself, FUS/TLS, progranulin, tau, APP, synuclein, Cdk5, huntingtin, presenilin, PrP, sirtuin, SOD, TAR DNA binding protein, and ataxin1 and 2.
This study is an important advance in the field and represents a first step toward a comprehensive understanding of the biological functions of TDP-43 and how this RNA binding protein is involved in neurodegenerative disease. It appears from the present study that the physiological functions of TDP-43 are quite wide and involve numerous diverse RNAs in neurons. Additional experiments will be required to fully validate the current results, but the present findings are fascinating and encouraging. Although it is not yet clear as to the level that the authors' results may inform about novel therapeutic approaches for neurodegenerative diseases, the hope is that the information provided in this study will help move toward the identification of novel targets of future drugs for the treatment or prevention of neurodegeneration.