Laura Cimatti, PhD

Laura Cimatti, PhD

E-Mail: laura.cimatti@univie.ac.at
Department of Chromosome Biology

Project: "FILEDCARM" - Impact of Filamin RNA Editing on Carcinogenesis and Metastasis

Discoveries in the last decade remarkably changed our perception of gene expression and development, pinpointing RNA molecules as main cellular regulators. In fact, RNA diversity lies at the base of biological complexity through several processes, from alternative splicing to non-coding transcripts. In this scenario Adenosine to Inosine (A-to-I) RNA editing emerges as another layer of transcriptome diversification and regulation of gene expression. But many questions about RNA editing remain to be answered, among them the physiological significance of recoding, the identification of regulatory factors and the involvement in diseases. A-to-I editing has been demonstrated to be severely deregulated in cancer. However, its direct role in cancer has only been considered marginally and was investigated globally.

Filamins A and B (FLNA and FLNB) are actin-crosslinking proteins that are important for many cellular processes, including cytoskeletal reorganization, adhesion, migration and intracellular trafficking. The mRNAs encoding FLNA and FLNB undergo A-to-I RNA editing, leading to a highly conserved Q to R amino acid exchange at the identical position in either protein. Recently, FLNA role has come under scrutiny for its involvement in cancer development and progression, and for its overexpression in multiple types of cancer (prostate, breast, lung, hemangiomas, colon, melanoma, and neuroblastoma). Interestingly, deregulation of Filamin A expression in cancer shows different outcomes. Originally revealed as a cancer-promoting protein involved in invasion and metastasis, recent studies show that FLNA can also prevent tumor formation or progression. Due to its involvement in cell migration and its effect on tumors, FLNA is very likely a valuable cancer prognostic marker and potential therapeutic target.

With her INDICAR project Laura focus on the effect of transcript-specific editing on cancer. The analysis of Filamin RNA editing impact on cell migration, cancer initiation, proliferation and progression to malignancy has the final goal to explain FLNA dual role in cancer. This will be achieved thanks to the first mouse model in which only the Filamin A editing has been deleted (generated by Prof. Michael Jantsch group).

Publications

  • Zucchelli S, Cotella D, Takahashi H, Carrieri C, Cimatti L, Fasolo F, Jones MH, Sblattero D, Sanges R, Santoro C, Persichetti F, Carninci P, Gustincich S. SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA Biology. 2015 Aug 3;12(8):771-9.

  • Zucchelli S*, Fasolo F*, Russo R, Cimatti L, Patrucco L, Takahashi H, Jones MH, Santoro C, Sblattero D, Cotella D, Persichetti F, Carninci P, Gustincich S. SINEUPs are modular antisense long-non coding RNAs that increase synthesis of target proteins in cells. Frontiers in Cellular Neuroscience, 2015 May 13;9:174. *Equal contribution.

  • 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. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature (2012) 491(7424):454-7. *Equal contribution to this work.

  • De Crignis E, Re MC, Cimatti L, Zecchi L, Gibellini D. HIV-1 and HCV detection in dried blood spots by SYBR Green multiplex real-time RT-PCR. Journal of Virological Methods (2010) 165(1):51-6.

  • Borderi M, Gibellini D, Vescini F, De Crignis E, Cimatti L, Biagetti C, Tampellini L, Re MC. Metabolic bone disease in HIV infection. AIDS (2009) 23(11):1297-310.

  • Gibellini D, De Crignis E, Ponti C, Cimatti L, Borderi M, Tschon M, Giardino R, Re MC. HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFα activation. Journal of Medical Virology (2008) 80(9):1507-14.

  • De Crignis E, Cimatti L, Borderi M, Gibellini D, Re MC. Bone alterations during HIV infection. New Microbiologica (2008) 31(2):155-64.

  • Gibellini D, Borderi M, De Crignis E, Cicola R, Cimatti L, Vitone F, Chiodo F, Re MC. HIV-1 DNA load analysis in peripheral blood lymphocytes and monocytes from naïve and HAART-treated individuals. The Journal of Infection (2008) 56(3):219-25.