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PDBsum entry 4yh8
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References listed in PDB file
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Key reference
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Title
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A novel 3' Splice site recognition by the two zinc fingers in the u2af small subunit.
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Authors
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H.Yoshida,
S.Y.Park,
T.Oda,
T.Akiyoshi,
M.Sato,
M.Shirouzu,
K.Tsuda,
K.Kuwasako,
S.Unzai,
Y.Muto,
T.Urano,
E.Obayashi.
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Ref.
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Genes Dev, 2015,
29,
1649-1660.
[DOI no: ]
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PubMed id
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Abstract
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The pre-mRNA splicing reaction of eukaryotic cells has to be carried out
extremely accurately, as failure to recognize the splice sites correctly causes
serious disease. The small subunit of the U2AF heterodimer is essential for the
determination of 3' splice sites in pre-mRNA splicing, and several
single-residue mutations of the U2AF small subunit cause severe disorders such
as myelodysplastic syndromes. However, the mechanism of RNA recognition is
poorly understood. Here we solved the crystal structure of the U2AF small
subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif
(RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs
are positioned side by side on the β sheet of the RRM domain. Further
mutational analysis revealed that the ZFs bind cooperatively to the target RNA
sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and
does not itself contact the RNA directly. This completely novel and unexpected
mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing
errors caused by mutations of this highly conserved protein.
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