Short cryptic exons mediate recursive splicing in Drosophila Journal Article


Authors: Joseph, B.; Kondo, S.; Lai, E. C.
Article Title: Short cryptic exons mediate recursive splicing in Drosophila
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. © 2018 The Author(s).
Journal Title: Nature Structural and Molecular Biology
Volume: 25
Issue: 5
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2018-05-01
Start Page: 365
End Page: 371
Language: English
DOI: 10.1038/s41594-018-0052-6
PROVIDER: scopus
PUBMED: 29632374
PMCID: PMC6709686
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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  1. Eric C Lai
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  2. Brian Jude Joseph
    9 Joseph