microRNA in the nervous system

Proteina Dicer (Cogoni) (sml)
The protein “dicer” is expressed selectively in neurons (red) and not in astrocytes (green). Blue is a nuclear staining for identification of all cells.

In the last years it has become evident that small regulatory RNAs play an important role in regulating gene expression. Small RNAs have been observed to act at different levels controlling either the translation and degradation of mRNAs or the transcription by modifiyng the chromatin structure. Eukaryotic cells are able to recognize and process double stranded RNA (dsRNA) in short RNAs 21-25 nucleotides in length (called short interfering RNAs: siRNAs).

The siRNAs are part of a complex called RISC (RNA-indiced silencing complex) that uses siRNAs as guide to induce sequence specific degradation of homologous RNAs. Small RNAs are also produced by processing of short hairpin-like RNA encoded in the genome. These endogenous small RNAs, called microRNAs (miRNA), function to control the expression of endogenous genes by regulating the translation of target mRNAs that show partially complementary regions located at the 3´ UTR.

Hundreds miRNAs have been identified in mammals and, although the biological functions of most miRNAs are unknown, miRNAs are predicted to regulate up to 30% of the genes within the human genome. Interestingly, many miRNAs are specifically expressed in the nervous system, suggesting that the gene regulation networks based on miRNAs may be particularly relevant in neuronal cells. In fact, modulation of mRNA translation and consequently protein synthesis at specific cellular sites, as synapses, has been proposed to be relevant in neurons for biological processes as memory-related synaptic plasticity and dendridic development.

We are addressing the role of the RNA-mediated gene silencing machinery in neurons, using different approaches including: the biochemical characterization of RISC in neuronal cells with the aim to indentify new neuronal components of RISC and the identification of synaptic microRNAs.