Research Groups

Human Molecular Genetics

Research Interests and Description

Group Leader: Franco Pagani, MD, PhD

Group Members

Research Interests

Regulation of pre-mRNA processing in human diseases.

Description of Research

The research of the Human Molecular Genetics group is focused on normal and pathological pre-mRNA processing with the aim to identify novel therapeutic strategies for correction of splicing defects.
We are exploring the molecular basis of splicing defects associated to coagulation deficiencies (hemophilia), cystic fibrosis, Spinal Muscular Atrophy and Netherton Syndrome. Our major interest is understanding how defects in non canonical splicing regulatory elements induce aberrant processing of pre-mRNA and develop appropriate strategies for splicing correction. We recently found that precise engineering of the U1 core spliceosomal RNA particle has a therapeutic potential in pathologies associated to exon-skipping mutations. Modified variants of U1 snRNA (Exon Specific U1 snRNAs) that binds by complementarity to intronic sequences downstream the 5'ss can correct exon skipping defects caused by different types of mutations. We are exploring this novel therapeutic strategy in cellular and animal models of coagulation defects, of Spinal Muscular Atrophy and Netherthon syndrome and understand the molecular mechanism involved. Part of the work is also dedicated to the analysis of a novel class of pri-miRNAs we have recently identified, whose hairpins present on pre-mRNA overlap with the splice site (Splice Site Overlapping miRNA) .

Research support is also provided by TELETHON, Italian Cystic Fibrosis Foundation , AFM and Italian Ministry of  Health

Graduate Student and Postdoctoral Positions: Enquiries with CV welcome

Recent Publications

Rogalska, M.E., Tajnik, M., Licastro, D., Bussani, E., Camparini, L., Mattioli, C., Pagani, F. 2016. Therapeutic activity of modified U1 core spliceosomal particles. Nat Commun, 7, 11168. PubMed Link

Tajnik, M., Rogalska, M.E., Bussani, E., Barbon, E., Balestra, D., Pinotti, M., Pagani, F. 2016. Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function. PLoS Genet, 12, e1006082. PubMed link

Dal Mas, A., Rogalska, M.E., Bussani, E., Pagani, F. 2015. Improvement of SMN2 Pre-mRNA Processing Mediated by Exon-Specific U1 Small Nuclear RNA. Am J Hum Genet, 96, 93-103 PubMed link

Dal Mas, A., Fortugno, P., Donadon, I., Levati, L., Castiglia, D., Pagani, F. 2015. Exon-Specific U1s Correct SPINK5 Exon 11 Skipping Caused by a Synonymous Substitution That Affects a Bi-Functional Splicing Regulatory Element. Hum Mutat, 10.1002/humu.22762 PubMed link

Mattioli, C., Pianigiani, G., Pagani, F. 2014. Cross talk between spliceosome and microprocessor defines the fate of pre-mRNA. Wiley Interdiscip Rev RNA, 5, 647-658 PubMed link

Mattioli, C., Pianigiani, G., De Rocco, D., Bianco, A.M., Cappelli, E., Savoia, A., Pagani, F. 2014. Unusual splice site mutations disrupt FANCA exon 8 definition. Biochim Biophys Acta, 1842, 1052-1058 PubMed link

Cod. Fisc. 90031700322 tl_files/trieste pics/5permille .png

AREA Science Park
Padriciano 99
34149 Trieste, ITALY
Tel: +39-040-37571
Fax: +39-040-226555
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