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Showing papers by "Franco Pagani published in 2014"


Journal ArticleDOI
TL;DR: The ability of the spliceosomal small nuclear RNA U1 to rescue pre‐mRNA splicing impaired by mutations makes it an attractive therapeutic molecule, but the effects of U1snRNAs in vivo remain unknown.

36 citations


Journal ArticleDOI
TL;DR: The outcome of a pre‐mRNA transcript and its final handling as miRNA or mRNA substrate can be frequently closely connected to the functional relationships between diverse pre-mRNA processing events.
Abstract: The spliceosome and the microprocessor complex (MPC) are two important processing machineries that act on precursor (pre)-mRNA. Both cleave the pre-mRNA to generate spliced mature transcripts and microRNAs (miRNAs), respectively. While spliceosomes identify in a complex manner correct splice sites, MPCs typically target RNA hairpins (pri-miRNA hairpins). In addition, pre-mRNA transcripts can contain pri-miRNA-like hairpins that are cleaved by the MPC without generating miRNAs. Recent evidence indicates that the position of hairpins on pre-mRNA, their distance from splice sites, and the relative efficiency of cropping and splicing contribute to determine the fate of a pre-mRNA. Depending on these factors, a pre-mRNA can be preferentially used to generate a miRNA, a constitutively or even an alternative spliced transcript. For example, competition between splicing and cropping on splice-site-overlapping miRNAs (SO miRNAs) results in alternative spliced isoforms and influences miRNA biogenesis. In several cases, the outcome of a pre-mRNA transcript and its final handling as miRNA or mRNA substrate can be frequently closely connected to the functional relationships between diverse pre-mRNA processing events. These events are influenced by both gene context and physiopathological conditions.

26 citations


Journal ArticleDOI
TL;DR: The results highlight the importance of performing splicing functional assay for correct identification of disease-causing mechanism of genomic variants and provide mechanistic insights on how these two FANCA mutations affect exon 8 definition.

15 citations