A novel role for shuttling SR proteins in mRNA translation.
The Ser-Arg-rich (SR) proteins comprise a large family of nuclear phosphoproteins that are required for constitutive and alternative splicing. A subset of SR proteins shuttles continuously between the nucleus and the cytoplasm, suggesting that the role of shuttling SR proteins in gene expression may not be limited to nuclear pre-mRNA splicing, but may also include unknown cytoplasmic functions. Here, we show that shuttling SR proteins, in particular SF2/ASF, associate with translating ribosomes and stimulate translation when tethered to a reporter mRNA in Xenopus oocytes. Moreover, SF2/ASF enhances translation of reporter mRNAs in HeLa cells, and this activity is dependent on its ability to shuttle from the nucleus to the cytoplasm and is increased by the presence of an exonic-splicing enhancer. Furthermore, SF2/ASF can stimulate translation in vitro using a HeLa cell-free translation system. Thus, the association of SR proteins with translating ribosomes, as well as the stimulation of translation both in vivo and in vitro, strongly suggest a role for shuttling SR proteins in translation. We propose that shuttling SR proteins play multiple roles in the posttranscriptional expression of eukaryotic genes and illustrate how they may couple splicing and translation.
Sanford
Jeremy R
JR
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom.
Gray
Nicola K
NK
Beckmann
Karsten
K
Cáceres
Javier F
JF
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism
D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D008156:Luciferases