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Comparative analysis detects dependencies among the 5 splice-site positions
 

Summary: Comparative analysis detects dependencies
among the 5 splice-site positions
IDO CARMEL, SAAR TAL, IDA VIG, and GIL AST
Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
ABSTRACT
Human­mouse comparative genomics is an informative tool to assess sequence functionality as inferred from its conservation
level. We used this approach to examine dependency among different positions of the 5 splice site. We compiled a data set of
50,493 homologous human­mouse internal exons and analyzed the frequency of changes among different positions of homolo-
gous human­mouse 5 splice-site pairs. We found mutual relationships between positions +4 and +5, +5 and +6, -2 and +5, and
-1 and +5. We also demonstrated the association between the exonic and the intronic positions of the 5 splice site, in which
a stronger interaction of U1 snRNA and the intronic portion of the 5 splice site compensates for weak interaction of U1 snRNA
and the exonic portion of the 5 splice site, and vice versa. By using an ex vivo system that mimics the effect of mutation in the
5 splice site leading to familial dysautonomia, we demonstrated that U1 snRNA base-pairing with positions +6 and -1 is the
only functional requirement for mRNA splicing of this 5 splice site. Our findings indicate the importance of U1 snRNA
base-pairing to the exonic portion of the 5 splice site.
Keywords: mRNA splicing; 5 splice site; U1 snRNA; mutual relationship; familial dysautonomia; comparative genomics
INTRODUCTION
In mRNA splicing, the 5 splice site (5 ss) is recognized by
three small nuclear ribonuclear particles (snRNPs)--a com-
plex of small nuclear RNA (snRNA) and proteins. First, U1

  

Source: Ast, Gil - Department of Molecular Genetics and Biochemistry, Tel Aviv University

 

Collections: Biology and Medicine