Trafficking of mRNAs containing ALREX-promoting elements through nuclear speckles.
In vertebrates, the majority of mRNAs that encode secreted, membrane-bound or mitochondrial proteins contain RNA elements that activate an alternative mRNA nuclear export (ALREX) pathway. Here we demonstrate that mRNAs containing ALREX-promoting elements are trafficked through nuclear speckles. Although ALREX-promoting elements enhance nuclear speckle localization, additional features within the mRNA largely drive this process. Depletion of two TREX-associated RNA helicases, UAP56 and its paralog URH49, or inhibition of the TREX-associated nuclear transport factor, TAP, not only inhibits ALREX, but also appears to trap these mRNAs in nuclear speckles. mRNAs that contain ALREX-promoting elements associate with UAP56 in vivo. Finally, we demonstrate that mRNAs lacking a poly(A)-tail are not efficiently exported by the ALREX pathway and show enhanced association with nuclear speckles. Our data suggest that within the speckle, ALREX-promoting elements, in conjunction with the poly(A)-tail, likely stimulate UAP56/URH49 and TAP dependent steps that lead to the eventual egress of the export-competent mRNP from these structures.
Department of Biochemistry; University of Toronto; Toronto, ON Canada; Division of Integrated Life Science; Graduate School of Biostudies; Kyoto University; Kyoto, Japan.
Abdalla
A
Akef
Hui
H
Zhang
Seiji
S
Masuda
Alexander F
AF
Palazzo
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger
ALREX; TAP/NXF1; TREX; UAP56; mRNA nuclear export; nuclear speckles; poly(A)-tail