Noncoding rnas in neurons.

Lab meeting - 28th October 2009

Main Project:
Secondary Project: Piwi proteins and piRNAs.

Rodrigo Louro

Characterization of neuronal noncoding RNA-protein complexes expressed during axonal injury

Rodrigo Louro

Aim

Neuronal ncRNPs in axonal injury

The designed approach aim to provide insights into the mechanism of action and biological role ncRNA-protein complexes in the normal and injured mammalian brain. •

Isolate somal and axonal compartments - Microfluidics Chambers (Taylor et al. 2005; Park et al. 2006) to idependently perform gene expression analysis;

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Identify using Solexa sequencing:
1- RNAs (ncRNAs and mRNAs) preferentially localized in axons (and in soma); 2- RNAs synthesized in response to axonal injury (and regeneration) to study their involvement in neurodegenerative diseases.

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Other biochemical techniques will identify RBP complement of a few ncRNAs.

Background •
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Neuronal ncRNPs in axonal injury

Regulatory ncRNAs seem to be pivotal to the evolution of complex attributes – different species have a very similar set (with a similar number) of protein-coding genes; ncRNAs control gene expression acting at transcriptional, post-transcriptional, and translational levels. Chromatin rearrangements (Plath et al. 2003; Rinn et al. 2007), promoter assembly interference (Martianov et al. 2007; Wang et al. 2008), alternative splicing (Yan et al. 2005; Hirose et al. 2006), and repression (Pillai et al. 2007) or activation of translation (Vasudevan et al. 2007); Cell diversity, environmental responsiveness, neural connections, and synaptic plasticity - the human/mammalian brain - the most extreme complexity among organs (Abrous et al. 2005); ncRNAs are overly represented in the nervous system (Mehler and Mattick 2006); Axons can be very long (e.g. ~1m single cell sciatic nerve) - post-transcriptional regulation in neurons must be highly compartmentalized and respond to local environment;

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