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The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway.

Abstract：

:Translational control is frequently exerted at the stage of mRNA recruitment to the initiating ribosome. We have reconstituted mRNA recruitment to the 43S preinitiation complex (PIC) using purified S. cerevisiae components. We show that eIF3 and the eIF4 factors not only stabilize binding of mRNA to the PIC, they also dramatically increase the rate of recruitment. Although capped mRNAs require eIF3 and the eIF4 factors for efficient recruitment to the PIC, uncapped mRNAs can be recruited in the presence of eIF3 alone. The cap strongly inhibits this alternative recruitment pathway, imposing a requirement for the eIF4 factors for rapid and stable binding of natural mRNA. Our data suggest that the 5' cap serves as both a positive and negative element in mRNA recruitment, promoting initiation in the presence of the canonical group of mRNA handling factors while preventing binding to the ribosome via an aberrant, alternative pathway requiring only eIF3.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Mitchell SF,Walker SE,Algire MA,Park EH,Hinnebusch AG,Lorsch JR

doi

10.1016/j.molcel.2010.08.021

subject

Has Abstract

pub_date

2010-09-24 00:00:00

pages

950-62

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(10)00631-3

journal_volume

39

pub_type

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