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Exosome cofactor hMTR 4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export
Author(s) -
Fan Jing,
Kuai Bin,
Wu Guifen,
Wu Xudong,
Chi Binkai,
Wang Lantian,
Wang Ke,
Shi Zhubing,
Zhang Heng,
Chen She,
He Zhisong,
Wang Siyuan,
Zhou Zhaocai,
Li Guohui,
Cheng Hong
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201696139
Subject(s) - exosome complex , rna , biology , exosome , microbiology and biotechnology , messenger rna , rna binding protein , nuclear export signal , signal transducing adaptor protein , cytoplasm , non coding rna , biochemistry , microrna , microvesicles , gene , signal transduction
The exosome is a key RNA machine that functions in the degradation of unwanted RNA s. Here, we found that significant fractions of precursors and mature forms of mRNA s and long noncoding RNA s are degraded by the nuclear exosome in normal human cells. Exosome‐mediated degradation of these RNA s requires its cofactor hMTR 4. Significantly, hMTR 4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR 4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS 2, a component of the cap‐binding complex ( CBC ), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm. Together, our results indicate that the competition between hMTR 4 and ALYREF determines exosome recruitment and functions in creating balanced nuclear RNA pools for degradation and export.