Journal
NUCLEUS
Volume 4, Issue 4, Pages 326-340Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/nucl.26052
Keywords
nuclear speckles; mRNA nuclear export; poly(A)-tail; ALREX; TREX; UAP56; TAP/NXF1
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Funding
- Canadian Institutes of Health Research [FRN 102725]
- Ontario Graduate Scholarship
- Grants-in-Aid for Scientific Research [23380059] Funding Source: KAKEN
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In vertebrates, the majority of mRNAs that encode secreted, membrane-bound or mitochondrial proteins contain RNA elements that activate an alternative m RNA nuclear export (ALR.EX) 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 m RNA 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 rriFINP from these structures.
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