Neurogenomics is presently at a very exciting crossroad since recent discoveries have challenged the classic model of gene organization and information flow providing potential new regulatory layers of neuronal cell function.
Results from ENCODE and the FANTOM projects have shown that the majority of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes long non-coding RNA (lncRNA) and Transposable Elements (TE), such as SINEs (short interspersed nuclear elements) and LINEs (long interspersed nuclear elements). TEs can form independent transcriptional units or be embedded in mRNA or lncRNAs. Surprisingly, the large majority of genes share their genomic region with another gene on the opposite filament forming Sense/Antisense pairs. Furthermore, transcription and retrotransposition of LINEs and SINEs occur during neurogenesis creating somatic differences in genomic DNA sequences of neuronal cells.
The laboratory of Non-coding RNA and RNA-based therapeutics presents two research lines:
- SINEUPS: a new functional class of long non-coding RNAs that activate translation.
- The role of TEs in brain function and disease.
- SINEUPs: They are a new functional class of natural and synthetic lncRNAs that activate translation in a gene-dependent fashion. We are studying the regulatory role of natural SINEUPs in brain function and the use of synthetic SINEUPs as RNA therapeutics of neurodegenerative diseases.
- TEs: We are currently investigating the role of the expression and mobilization of TEs in brain function and neurodegenerative diseases. To this purpose we are developing technologies for the identification of structural variations in neurons.
- Zucchelli S, Cotella D, Takahashi H, Carrieri C, Cimatti L, Jones MH, Sblattero D, Sanges R, Santoro C, Persichetti F, Carninci P# and Gustincich S. (2015). SINEUPs: a new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA biology 12:771-79.
- Zucchelli S, Fasolo F, Russo R, Cimatti L, Persichetti F, Jones M, Santoro C, Cotella D, Carninci P, Gustincich S. (2015). SINEUPs are modular antisense long-non coding RNAs that increase synthesis of target proteins in cells. Front Cell Neurosci 9:174.
- FANTOM Consortium and the RIKEN PMI and CLST (DGT) et al., (2014). A promoter-level mammalian expression atlas. Nature 507(7493):462-70.
- Andersson R at al., (2014). An atlas of active enhancers across human cell types and tissues. Nature 507(7493):455-61.
- Carrieri C*, Cimatti L*, Biagioli M, Beugnet A, Zucchelli S, Fedele S, Pesce E, Ferrer I, Collavin L, Santoro C, Forrest AR, Carninci P, Biffo S, Stupka E, Gustincich S. (2012). Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. *These authors equally contributed to the work. Nature 491(7424):454-7.