Splicing of doublesex pre-mRNA (pp. 439-441)
Faustino N.A. and Cooper T.A. (2003) Pre-mRNA splicing and human disease. Genes & Devel. 17: 419-437
Hirose Y. and Manley J.L. (2000) RNA polymerase II and the integration of nuclear events. Genes & Devel. 14: 1415-1429
Maquat L.E. and Carmichael G.G. (2001) Quality control of mRNA function. Cell 104: 173-176
Gallouzi I.E. and Steitz J.A. 2001) Delineation
of mRNA export pathways by the use of cell-permeable peptides. Science
The transport of mRNAs from the nucleus to the cytoplasm involves adapter proteins that bind the mRNA as well as receptor proteins that interact with the nuclear pore complex. The investigators use inhibitory peptides to show that a given mRNA may use overlapping (partially redundant) pathways for leaving the nucleus. For example, HuR protein serves as an adapter for c-fos mRNA export through two pathways. One involves the HuR shuttling domain, HNS, which exhibits a heat shock-sensitive interaction with transportin 2 (Trn2); the other involves two protein ligands of HuR - pp32 and APRIL - which contain leucine-rich nuclear export signals (NES) recognized by the export receptor CRM1. Heterokaryon and in situ hybridization experiments reveal that the inhibitory peptides selectively block the nucleocytoplasmic shuttling of their respective adapter proteins without perturbing the overall cellular distribution of polyadenylated mRNAs.
Horabin J.I. and Schedl P. (1996) Splicing of the drosophila Sex-lethal early transcripts involves exon skipping that is independent of Sex-lethal protein. RNA 2: 1-10.
Nagengast A.A., Stitzinger S.M., Tseng C.H.,
Mount S.M. and Salz H.K. (2003) Sex-lethal splicing
autoregulation in vitro: interactions between SEX-LETHAL, the U1
snRNP and UsAF underlie male exon skipping. Development 130:
The investigators provide genetic and biochemical evidence that the Sexlethal protein causes the skipping of exon 3 in Sxl pre-mRNA by binding to both the acceptor and the donor site of this exon.
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