Transient translational silencing by reversible mRNA deadenylation.
Tissue-type plasminogen activator (tPA) mRNA is stored, stable and untranslated, in the cytoplasm of fully grown primary mouse oocytes. Dormancy is associated with an unusually short poly(A) tail, and poly(A) tail elongation controls tPA mRNA translational activation during meiotic maturation. Here we show that the nuclear transcript of this mRNA is extensively polyadenylated and that primary oocytes contain a deadenylating activity capable of silencing the cytoplasmic message. The sequence determinants that control deadenylation and polyadenylation overlap; this AU-rich region thus serves as an adenylation control element (ACE). The translation of a reporter mRNA in primary oocytes is prevented upon inclusion of an ACE in its 3' untranslated region. Therefore, the stage-specific regulation of poly(A) tail length accounts for the regulated synthesis of tPA in oocytes, and reversible deadenylation provides a mechanism for the translational control of dormant mRNAs.
Huarte
J
J
Institute of Histology and Embryology, University of Geneva Medical School, Switzerland.
Stutz
A
A
O'Connell
M L
ML
Gubler
P
P
Belin
D
D
Darrow
A L
AL
Strickland
S
S
Vassalli
J D
JD
D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008540:Meiosis; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009865:Oocytes / Q000502:physiology*; D011061:Poly A / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011061:Poly A; D010959:Tissue Plasminogen Activator