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Citation
Joseph, B., Kondo, S., Lai, E.C. (2018). Short cryptic exons mediate recursive splicing in Drosophila.  Nat. Struct. Mol. Biol. 25(5): 365--371.
FlyBase ID
FBrf0238837
Publication Type
Research paper
Abstract
Many long Drosophila introns are processed by an unusual recursive strategy. The presence of ~200 adjacent splice acceptor and splice donor sites, termed ratchet points (RPs), were inferred to reflect 'zero-nucleotide exons', whose sequential processing subdivides removal of long host introns. We used CRISPR-Cas9 to disrupt several intronic RPs in Drosophila melanogaster, some of which recapitulated characteristic loss-of-function phenotypes. Unexpectedly, selective disruption of RP splice donors revealed constitutive retention of unannotated short exons. Assays using functional minigenes confirm that unannotated cryptic splice donor sites are critical for recognition of intronic RPs, demonstrating that recursive splicing involves the recognition of cryptic RP exons. This appears to be a general mechanism, because canonical, conserved splice donors are specifically enriched in a 40-80-nt window downstream of known and newly annotated intronic RPs and exhibit similar properties to a broadly expanded class of expressed RP exons. Overall, these studies unify the mechanism of Drosophila recursive splicing with that in mammals.
PubMed ID
PubMed Central ID
PMC6709686 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Struct. Mol. Biol.
    Title
    Nature Structural and Molecular Biology
    Publication Year
    2004-
    ISBN/ISSN
    1545-9993 1545-9985
    Data From Reference
    Genes (5)
    Cell Lines (1)