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The major mRNA‐associated protein YB‐1 is a potent 5′ cap‐dependent mRNA stabilizer
Author(s) -
Evdokimova Valentina,
Ruzanov Peter,
Imataka Hiroaki,
Raught Brian,
Svitkin Yuri,
Ovchinnikov Lev P.,
Sonenberg Nahum
Publication year - 2001
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 - 10.1093/emboj/20.19.5491
Subject(s) - messenger rna , biology , gene silencing , p bodies , eif4e , translation (biology) , protein biosynthesis , microbiology and biotechnology , gene expression , nonsense mediated decay , rna , gene , biochemistry , rna splicing
mRNA silencing and storage play an important role in gene expression under diverse circumstances, such as throughout early metazoan development and in response to many types of environmental stress. Here we demonstrate that the major mRNA‐associated protein YB‐1, also termed p50, is a potent cap‐dependent mRNA stabilizer. YB‐1 addition or overexpression dramatically increases mRNA stability in vitro and in vivo , whereas YB‐1 depletion results in accelerated mRNA decay. The cold shock domain of YB‐1 is responsible for the mRNA stabilizing activity, and a blocked mRNA 5′ end is required for YB‐1‐mediated stabilization. Significantly, exogenously added YB‐1 destabilizes the interaction of the cap binding protein, eIF4E, with the mRNA cap structure. Conversely, sequestration of eIF4E from the cap increases the association of endogenous YB‐1 with mRNA at or near the cap, and significantly enhances mRNA stability. These data support a model whereby down‐regulation of eIF4E activity or increasing the YB‐1 mRNA binding activity or concentration in cells activates a general default pathway for mRNA stabilization.