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|Title: ||TDP-43 regulates the Microprocessor complex activity during in vitro neuronal differentiation|
|Authors: ||DI CARLO, VALERIO|
|Tutor: ||CUTRUZZOLA', FRANCESCA|
|Issue Date: ||21-Jan-2014|
|Abstract: ||TDP-43 is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events.
In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression.
Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate-specificity of the microprocessor complex and provide new insights onto TDP-43 as a key player in neuronal differentiation.|
|Description: ||PhD thesis|
|Research interests: ||biologia molecolare|
|Appears in PhD:||SCIENZE PASTEURIANE|
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|PhDThesis Di Carlo.pdf||PhD thesis Di Carlo||1.74 MB||Adobe PDF|
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