Serine/arginine-rich splicing factor 3 (SRSF3), a member of the serine/arginine 
(SR)-rich family of proteins, regulates both alternative splicing of pre-mRNA 
and export of mature mRNA from the nucleus. Although its role in nuclear mRNA 
processing is well understood, the mechanism by which it alters the fate of 
cytoplasmic mRNA molecules remains elusive. Here, we provide evidence that SRSF3 
not only regulates the alternative splicing pattern of programmed cell death 4 
(PDCD4) mRNA, but also modulates its translational efficiency in the cytoplasm 
by lowering translation levels. We observed a marked increase in PDCD4 mRNA in 
translating polysome fractions upon silencing of SRSF3, and, conversely, ectopic 
overexpression of SRSF3 shifted PDCD4 mRNA into non-translating ribosomal 
fractions. In live cells, SRSF3 colocalized with PDCD4 mRNA in P-bodies (PBs), 
where translationally silenced mRNAs are deposited, and this localization was 
abrogated upon SRSF3 silencing. Furthermore, using two different reporter 
systems, we showed that SRSF3 interacts directly with PDCD4 mRNA and mediates 
translational repression by binding to the 5'-untranslated region (5'-UTR). In 
summary, our data suggest that the oncogenic potential of SRSF3 might be 
realized, in part, through the translational repression of PDCD4 mRNA.