Title: An interpretable model of pre-mRNA splicing for animal and plant genes

Journal Article · · Science Advances
ORCiD logo [1]; ORCiD logo [2]
  1. Massachusetts Institute of Technology (MIT), Cambridge, MA (United States); , Massachusetts Institute of Technology, Cambridge, MA (United States)
  2. Massachusetts Institute of Technology (MIT), Cambridge, MA (United States)
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Pre-mRNA splicing is a fundamental step in gene expression, conserved across eukaryotes, in which the spliceosome recognizes motifs at the 3' and 5' splice sites (SSs), excises introns, and ligates exons. SS recognition and pairing is often influenced by protein splicing factors (SFs) that bind to splicing regulatory elements (SREs). Here, we describe SMsplice, a fully interpretable model of pre-mRNA splicing that combines models of core SS motifs, SREs, and exonic and intronic length preferences. We learn models that predict SS locations with 83 to 86% accuracy in fish, insects, and plants and about 70% in mammals. Learned SRE motifs include both known SF binding motifs and unfamiliar motifs, and both motif classes are supported by genetic analyses. Our comparisons across species highlight similarities between non-mammals, increased reliance on intronic SREs in plant splicing, and a greater reliance on SREs in mammalian splicing.

Research Organization:
Krell Institute, Ames, IA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
FG02-97ER25308
OSTI ID:
2471914
Journal Information:
Science Advances, Journal Name: Science Advances Journal Issue: 19 Vol. 10; ISSN 2375-2548
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

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