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

Abstract:

: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.

journal_name

RNA Biol

journal_title

RNA biology

authors

Hong KY,Lee SH,Gu S,Kim E,An S,Kwon J,Lee JB,Jang SK

doi

10.1080/15476286.2017.1280224

subject

Has Abstract

pub_date

2017-03-04 00:00:00

pages

370-377

issue

3

eissn

1547-6286

issn

1555-8584

journal_volume

14

pub_type

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