The bent conformation of poly(A)-binding protein induced by RNA-binding is required for its translational activation function

• Published in: RNA biology Vol. 14; no. 3; pp. 370 - 377
• Main Authors: Hong, Ka Young, Lee, Seung Hwan, Gu, Sohyun, Kim, Eunah, An, Sihyeon, Kwon, Junyoung, Lee, Jong-Bong, Jang, Sung Key
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 04.03.2017
• Subjects: Bent structure; Eukaryotic Initiation Factor-4G - metabolism; Humans; Multiprotein Complexes - metabolism; Mutation; PABP; PABP-eIF4G interaction; poly(A) tail; Poly(A)-Binding Proteins - chemistry; Poly(A)-Binding Proteins - genetics; Poly(A)-Binding Proteins - metabolism; Protein Binding; Protein Biosynthesis; Protein Conformation; Research Paper; Ribosomes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Structure-Activity Relationship; translation; translation; PABP; Bent structure; PABP-eIF4G interaction; poly(A) tail
• ISSN: 1547-6286; 1555-8584
• DOI: 10.1080/15476286.2017.1280224

A recent study revealed that poly(A)-binding protein (PABP) bound to poly(A) RNA exhibits a sharply bent configuration at the linker region between RNA-recognition motif 2 (RRM2) and RRM3, whereas free PABP exhibits a highly flexible linear configuration. However, the physiological role of the bent structure of mRNA-bound PABP remains unknown. We investigated a role of the bent structure of PABP by constructing a PABP variant that fails to form the poly(A)-dependent bent structure but maintains its poly(A)-binding activity. We found that the bent structure of PABP/poly(A) complex is required for PABP's efficient interaction with eIF4G and eIF4G/eIF4E complex. Moreover, the mutant PABP had compromised translation activation function and failed to augment the formation of 80S translation initiation complex in an in vitro translation system. These results suggest that the bent conformation of PABP, which is induced by the interaction with 3′ poly(A) tail, mediates poly(A)-dependent translation by facilitating the interaction with eIF4G and the eIF4G/eIF4E complex. The preferential binding of the eIF4G/eIF4E complex to the bent PABP/poly(A) complex seems to be a mechanism discriminating the mRNA-bound PABPs participating in translation from the idling mRNA-unbound PABPs.