Abstract:
T
issue-specific alternative pre-mRNA splicing is essen-
tial for increasing diversity of functionally different
gene products. In Caenorhabditis elegans, UNC-
60A and UNC-60B, nonmuscle and muscle isoforms of
actin depolymerizing factor (ADF)/cofilin, are expressed
by alternative splicing of unc-60 and regulate distinct
actin-dependent developmental processes. We report that
SUP-12, a member of a new family of RNA recognition
motif (RRM) proteins, including SEB-4, regulates muscle-
specific splicing of unc-60. In sup-12 mutants, expression of
UNC-60B is decreased, whereas UNC-60A is up-regulated
in muscle. sup-12 mutations strongly suppress muscle
defects in unc-60B mutants by allowing expression of
UNC-60A in muscle that can substitute for UNC-60B, thus
unmasking their functional redundancy. SUP-12 is ex-
pressed in muscle and localized to the nuclei in a speckled
pattern. The RRM domain of SUP-12 binds to several sites
of the unc-60 pre-mRNA including the UG repeats near
the 3 -splice site in the first intron. Our results suggest that
SUP-12 is a novel tissue-specific splicing factor and regu-
lates functional redundancy among ADF/cofilin isoforms.
