TY - JOUR
T1 - Cap-binding protein 4EHP effects translation silencing by microRNAs
AU - Chapat, Clement
AU - Jafarnejad, Seyed Mehdi
AU - Matta-Camacho, Edna
AU - Hesketh, Geoffrey G.
AU - Gelbart, Idit A.
AU - Attig, Jan
AU - Gkogkas, Christos G.
AU - Alain, Tommy
AU - Stern-Ginossar, Noam
AU - Fabian, Marc R.
AU - Gingras, Anne-Claude
AU - Duchaine, Thomas F.
AU - Sonenberg, Nahum
PY - 2017/5/23
Y1 - 2017/5/23
N2 - MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loopmRNA conformation that blocks translational initiation of miRNA targets.
AB - MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loopmRNA conformation that blocks translational initiation of miRNA targets.
UR - http://www.scopus.com/inward/record.url?scp=85019611996&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.1701488114
DO - https://doi.org/10.1073/pnas.1701488114
M3 - مقالة
SN - 0027-8424
VL - 114
SP - 5425
EP - 5430
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -