Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p

The yeast nuclear protein Yra1p is an essential export factor for mRNA. Yra1p interacts directly with the mRNA transport factor Mex67p/Mtr2p, which is associated with the nuclear pore. Here, we report a genetic interaction between YRA1 and SUB2, the gene for a DEAD box helicase involved in splicing. Mutation of SUB2 as well as its overexpression leads to a defect in mRNA export. Moreover, Yra1p and Sub2p bind directly to each other both in vivo and in vitro. Significantly, Sub2p and Mex67p/Mtr2p bind to the same domains of Yra1p, and the proteins compete for binding to Yra1p. Together, these data indicate that the spliceosomal component Sub2p is also important in mRNA export and may function to recruit Yra1p to the mRNA. Sub2p may then be displaced from Yra1p by the binding of Mex67p/Mtr2p, which participates in the export of mRNA through the nuclear pores.

[1]  M. Green,et al.  Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. , 2001, Genes & development.

[2]  M. Rieger,et al.  A Novel Complex of Nucleoporins, Which Includes Sec13p and a Sec13p Homolog, Is Essential for Normal Nuclear Pores , 1996, Cell.

[3]  R Grosschedl,et al.  ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function. , 1997, Genes & development.

[4]  M. Künzler,et al.  Yeast Los1p Has Properties of an Exportin-Like Nucleocytoplasmic Transport Factor for tRNA , 1998, Molecular and Cellular Biology.

[5]  D. Tollervey,et al.  Mex67p Mediates Nuclear Export of a Variety of RNA Polymerase II Transcripts* , 2000, The Journal of Biological Chemistry.

[6]  P. Bork,et al.  REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. , 2000, RNA.

[7]  R. Lührmann,et al.  Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores , 1997, The EMBO journal.

[8]  E. Hurt,et al.  The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans , 2000, Nature.

[9]  M. Rosbash,et al.  A block to mRNA nuclear export in S. cerevisiae leads to hyperadenylation of transcripts that accumulate at the site of transcription. , 2001, Molecular cell.

[10]  M. Green,et al.  A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins. , 1999, Molecular cell.

[11]  G. Dreyfuss,et al.  YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity. , 1997, RNA.

[12]  M. Mann,et al.  Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly , 2001, Nature.

[13]  J. Steitz,et al.  Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. , 2001, Molecular cell.

[14]  D. Tollervey,et al.  Identification of a Regulated Pathway for Nuclear Pre-mRNA Turnover , 2000, Cell.

[15]  K Strässer,et al.  Yra1p, a conserved nuclear RNA‐binding protein, interacts directly with Mex67p and is required for mRNA export , 2000, The EMBO journal.

[16]  D. Libri,et al.  Multiple roles for the yeast SUB2/yUAP56 gene in splicing. , 2001, Genes & development.

[17]  C. Guthrie,et al.  Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. , 2001, Genes & development.

[18]  J. Warner,et al.  The economics of ribosome biosynthesis in yeast. , 1999, Trends in biochemical sciences.