Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2.
The yeast Mex67-Mtr2 complex and its homologous metazoan counterpart TAP-p15 operate as nuclear export receptors by binding and translocating mRNA through the nuclear pore complexes. Here, we show how Mex67-Mtr2 can also function in the nuclear export of the ribosomal 60S subunit. Biochemical and genetic studies reveal a previously unrecognized interaction surface on the NTF2-like scaffold of the Mex67-Mtr2 heterodimer, which in vivo binds to pre-60S particles and in vitro can interact with 5S rRNA. Crucial structural requirements for this binding platform are loop insertions in the middle domain of Mex67 and Mtr2, which are absent from human TAP-p15. Notably, when the positively charged amino acids in the Mex67 loop are mutated, interaction of Mex67-Mtr2 with pre-60S particles and 5S rRNA is inhibited, and 60S subunits, but not mRNA, accumulate in the nucleus. Thus, the general mRNA exporter Mex67-Mtr2 contains a distinct electrostatic interaction surface for transporting 60S preribosomal cargo.
Yao
Wei
W
Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
Roser
Daniela
D
Köhler
Alwin
A
Bradatsch
Bettina
B
Bassler
Jochen
J
Hurt
Ed
E
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D019281:Dimerization; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034443:RNA Transport; D012335:RNA, Ribosomal / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
C106898:MEX67 protein, S cerevisiae; D026901:Membrane Transport Proteins; C480169:Mtr2 protein, S cerevisiae; C117894:NMD3 protein, S cerevisiae; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins