PAB1 self-association precludes its binding to Poly(A), thereby accelerating CCR4 deadenylation in vivo

Abstract

The mRNA deadenylation process, catalyzed by the CCR4 deadenylase, is known to be the major factor controlling mRNA decay rates in Saccharomyces cerevisiae. We have identified the proline-rich region and RRM1 domains of poly(A) binding protein (PAB1) as necessary for CCR4 deadenylation. Deletion of either of these regions but not other regions of PAB1 significantly reduced PAB1-PAB1 protein interactions, suggesting that PAB1 oligomerization is a required step for deadenylation. Moreover, defects in these two regions inhibited the formation of a novel, circular monomeric PAB1 species that forms in the absence of poly(A). Removal of the PAB1 RRM3 domain, which promoted PAB1 oligomerization and circularization, correspondingly accelerated CCR4 deadenylation. Circular PAB1 was unable to bind poly(A), and PABI multimers were severely deficient or unable to bind poly(A), implicating the PAB1 RNA binding surface as critical in making contacts that allow PABI self-association. These results support the model that the control of CCR4 deadenylation in vivo occurs in part through the removal of PABI from the poly(A) tail following its self-association into multimers and/or a circular species. Known alterations in the P domains of different PAB proteins and factors and conditions that affect PABI self-association would, therefore, be expected to be critical to controlling mRNA turnover in the cell.

Publication Date

9-1-2007

Journal Title

Molecular and cellular biology

Publisher

American Society for Microbiology

Digital Object Identifier (DOI)

10.1128/MCB.00734-07

Scientific Contribution Number

2285

Document Type

Article

Rights

© 2007, American Society for Microbiology.

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