Meccanismi di regolazione post-trascrizionale: ruolo delle ribonucleoproteine

Starting date
January 1, 2008
Duration (months)
48
Managers or local contacts
Romanelli Maria

Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent one of the most abundant classes of RNPs. They are involved in many crucial aspects of the control of gene expression. In particular, hnRNP type I (PTB) is known as a negative regulator of RNA processing, in the role of repressor of tissue-specific exons. The research plan focuses on the study of the role of hnRNP PTB, nPTB and Raver ribonucleproteins in the regulation of gene expression in muscular tissue. This program represents the natural follow up of a long sought and well documented interest of the research unit towards PTB and Raver proteins, which interact with PTB as co-repressors.
We plan to investigate their roles in the regulating alternative splicing of muscle-specific transcripts. The embrionic murine cell line C2C12 will be used as a model system for skeletal muscle differentiation. Various splicing variants of the cited hnRNPs will be characterized and quantified, at different differentiation stages of C2C12 cells in colture. We will then investigate on their role as repressors of tissue specific exons in transcripts from myogenic factors, such as MEF2 and from PKM2 and AXNA7 genes. Alternative exons of PKM2 and AXNA7 are in fact preferentially expressed in skeletal muscle. The involvement of PTB proteins in MEF2, PKM2 and AXNA7 genes alternative splicing will be tested by gene silencing (i.e.RNA interference) assays. Finally, we plan to complete the analysis of Raver genes controlling regions, by characterizing Raver 2 gene promoter.

Sponsors:

Ministero dell'Istruzione dell'Università e della Ricerca
Funds: assigned and managed by the department
Syllabus: FINANZMIUR - Finanziamento MIUR per la ricerca

Project participants

Erica Diani
Scholarship holder
Agnese Rita Filippa Tindara Filippello
Pamela Lorenzi
Technical-administrative staff
Publications
Title Authors Year
Post-transcriptional Gene Regulation: Role of the Polypyrimidine Tract-binding Protein (PTB) and Associated Factors in "From the hallowed halls of Herpesvirology". Romanelli MG.; Diani E. 2012
Molecular cloning and expression analyses of the RBM20 gene that is associated to familial dilated cardiomyopathy A. Filippello; P. Lorenzi; C. Morandi; M.G. Romanelli 2011
Expression, localization and functional role of ribonucleoproteins in myoblasts differentiation Diani E.; Filippello A.; Morandi C.; Romanelli MG 2010
Characterization and functional analysis of cis-acting elements of the human farnesyl diphosphate synthetase (FDPS) gene 5' flanking region. Romanelli, Maria; Lorenzi, Pamela; Sangalli, Antonella; Diani, Erica; Mottes, Monica 2009
Raver1 expression and alternative splicing events during skeletal muscle differentiation Diani Erica; Morandi Carlo; Romanelli Maria Grazia 2009

Activities

Research facilities