Translation Factors Promote the Formation of Two States of the Closed-loop MRNP

Overview

Journal Nature

Specialty Science

Date 2008 May 23

PMID 18496529

Citations 118

Authors

Nadia Amrani

Shubhendu Ghosh

David A Mangus

Allan Jacobson

Affiliations

Soon will be listed here.

Abstract

Efficient translation initiation and optimal stability of most eukaryotic messenger RNAs depends on the formation of a closed-loop structure and the resulting synergistic interplay between the 5' m(7)G cap and the 3' poly(A) tail. Evidence of eIF4G and Pab1 interaction supports the notion of a closed-loop mRNP, but the mechanistic events that lead to its formation and maintenance are still unknown. Here we use toeprinting and polysome profiling assays to delineate ribosome positioning at initiator AUG codons and ribosome-mRNA association, respectively, and find that two distinct stable (resistant to cap analogue) closed-loop structures are formed during initiation in yeast cell-free extracts. The integrity of both forms requires the mRNA cap and poly(A) tail, as well as eIF4E, eIF4G, Pab1 and eIF3, and is dependent on the length of both the mRNA and the poly(A) tail. Formation of the first structure requires the 48S ribosomal complex, whereas the second requires an 80S ribosome and the termination factors eRF3/Sup35 and eRF1/Sup45. The involvement of the termination factors is independent of a termination event.

Citing Articles

Yeast poly(A)-binding protein (Pab1) controls translation initiation in vivo primarily by blocking mRNA decapping and decay.

Poonia P, Valabhoju V, Li T, Iben J, Niu X, Lin Z Nucleic Acids Res. 2025; 53(5).

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Eukaryotic initiation factors eIF4F and eIF4B promote translation termination upon closed-loop formation.

Shuvalova E, Shuvalov A, Al Sheikh W, Ivanov A, Biziaev N, Egorova T Nucleic Acids Res. 2025; 53(5).

PMID: 40066881 PMC: 11894530. DOI: 10.1093/nar/gkaf161.

Pleiotropic effects of PAB1 deletion: Extensive changes in the yeast proteome, transcriptome, and translatome.

Mangkalaphiban K, Ganesan R, Jacobson A PLoS Genet. 2024; 20(9):e1011392.

PMID: 39236083 PMC: 11407637. DOI: 10.1371/journal.pgen.1011392.

Yeast poly(A)-binding protein (Pab1) controls translation initiation in vivo primarily by blocking mRNA decapping and decay.

Poonia P, Valabhoju V, Li T, Iben J, Niu X, Lin Z bioRxiv. 2024; .

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Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression.

Diamond P, McGlincy N, Ingolia N Mol Cell. 2024; 84(11):2119-2134.e5.

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