UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant.
Messenger RNA decay mediated by the c-fos major protein coding-region determinant of instability (mCRD) is a useful system for studying translationally coupled mRNA turnover. Among the five mCRD-associated proteins identified previously, UNR was found to be an mCRD-binding protein and also a PABP-interacting protein. Interaction between UNR and PABP is necessary for the full destabilization function of the mCRD. By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in vivo and also associated with UNR. Blocking either translation initiation or elongation greatly impeded poly(A) shortening and mRNA decay mediated by the mCRD, demonstrating that the deadenylation step is coupled to ongoing translation of the message. These findings suggest a model in which the mCRD/UNR complex serves as a "landing/assembly" platform for formation of a deadenylation/decay mRNA-protein complex on an mCRD-containing transcript. The complex is dormant prior to translation. Accelerated deadenylation and decay of the transcript follows ribosome transit through the mCRD. This study provides new insights into a mechanism by which interplay between mRNA turnover and translation determines the lifespan of an mCRD-containing mRNA in the cytoplasm.
Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston 77030, USA.
Tsung-Cheng
TC
Chang
Akio
A
Yamashita
Chyi-Ying A
CY
Chen
Yukiko
Y
Yamashita
Wenmiao
W
Zhu
Simon
S
Durdan
Avak
A
Kahvejian
Nahum
N
Sonenberg
Ann-Bin
AB
Shyu
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016762:Genes, fos; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D039102:Poly(A)-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
C515355:Ccr4 protein, mouse; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; C489441:UNR protein, mouse