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Fig. 2 | Molecular Cancer

Fig. 2

From: EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression

Fig. 2

Alternative Splicing regulation. a Scheme of the different AS modalities: (i) cassette exons; (ii) mutually exclusive exons; (iii) intron retention; (iv) alternative 5′ splice sites; (v) alternative 3′ splice sites; (vi) inclusion of a poison exon containing a premature stop-codon (yellow) leading to mRNA degradation through NMD. Precursor transcripts and final spliced products are shown. b AS regulation by combined action of trans- and cis-acting elements. Intronic and exonic splicing enhancers (ISE and ESE) promote the inclusion (+) of the AS exon (red) by providing the binding sites for activators (orange circles), whereas intronic and exonic splicing silencers (ISS and ESS) are bound by repressors (yellow circles) and promote exon skipping (-). Generally, ESE-bound SR factors stimulate the assembly of the splicesome on the variant exon or counteract the inhibitory activity of hnRNPs bound to ESS elements. On the contrary, hnRNPs interfere with the assembly of spliceosome to the variant exon leading to exon skipping. In addition, hnRNPs by binding ISSs located in the introns flanking a variant exon cause its looping out and skipping, whereas when bound to ESSs they may polymerize along the exon and displace the ESE-bound SR proteins (not shown). c Some members of the SR and hnRNP families mentioned in the text are shown with their characteristic domains. SR proteins have a modular structure with one or two RNA recognition motifs (RRM) in the N-terminus able to interact with the pre-mRNA, whereas at C-terminus all members of this family present a domain of variable length rich in serine-arginine dipeptides (RS domain) involved in protein-protein interactions with spliceosomal components. HnRNPs possess one or more RNA-binding domains associated with different “auxiliary” domains that are diverse in sequence and involved in sub-cellular localization or protein-protein interactions. Tissue-specific AS regulators (RBFOX, MBNL, ESRP and NOVA families) are indicated with their own RNA-binding domains

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