Therapeutic activity of modified U1 core spliceosomal particles

Malgorzata Ewa Rogalska, Mojca Tajnik, Danilo Licastro, Erica Bussani, Luca Camparini, Chiara Mattioli and Franco Pagani ()
Additional contact information
Malgorzata Ewa Rogalska: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology
Mojca Tajnik: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology
Danilo Licastro: CBM S.c.r.l., Area Science Park
Erica Bussani: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology
Luca Camparini: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology
Chiara Mattioli: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology
Franco Pagani: Human Molecular Genetics, International Centre for Genetic Engineering and Biotechnology

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Modified U1 snRNAs bound to intronic sequences downstream of the 5′ splice site correct exon skipping caused by different types of mutations. Here we evaluate the therapeutic activity and structural requirements of these exon-specific U1 snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model, ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion, SMN protein production and extends life span. In vitro, RNA mutant analysis and silencing experiments show that while U1A protein is dispensable, the 70K and stem loop IV elements mediate most of the splicing rescue activity through improvement of exon and intron definition. Our findings indicate that precise engineering of the U1 core spliceosomal RNA particle has therapeutic potential in pathologies associated with exon-skipping mutations.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms11168 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11168

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms11168

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().