The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression.
Nuclear export of mRNA is an essential process for eukaryotic gene expression. The TREX complex couples gene expression from transcription and splicing to mRNA export. Sub2, a core component of the TREX complex in yeast, has diversified in humans to two closely related RNA helicases, UAP56 and URH49. Here, we show that URH49 forms a novel URH49-CIP29 complex, termed the AREX (alternative mRNA export) complex, whereas UAP56 forms the human TREX complex. The mRNAs regulated by these helicases are different at the genome-wide level. The two sets of target mRNAs contain distinct subsets of key mitotic regulators. Consistent with their target mRNAs, depletion of UAP56 causes mitotic delay and sister chromatid cohesion defects, whereas depletion of URH49 causes chromosome arm resolution defects and failure of cytokinesis. In addition, depletion of the other human TREX components or CIP29 causes mitotic defects similar to those observed in UAP56- or URH49-depleted cells, respectively. Taken together, the two closely related RNA helicases have evolved to form distinct mRNA export machineries, which regulate mitosis at different steps.
Yamazaki
Tomohiro
T
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Fujiwara
Naoko
N
Yukinaga
Hiroko
H
Ebisuya
Miki
M
Shiki
Takuya
T
Kurihara
Tomoya
T
Kioka
Noriyuki
N
Kambe
Taiho
T
Nagao
Masaya
M
Nishida
Eisuke
E
Masuda
Seiji
S
D045744:Cell Line, Tumor; D002842:Chromatids / Q000235:genetics; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D034622:RNA Interference; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C105242:ALYREF protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C429143:SARNP protein, human; D014157:Transcription Factors; C498428:DDX39A protein, human; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases