eIF5A Functions Globally in Translation Elongation and Termination

Anthony P. Schuller, Colin Chih Chien Wu, Thomas E. Dever, Allen R. Buskirk, Rachel Green

Research output: Research - peer-reviewArticle

Abstract

The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches. Our data also show ribosome accumulation at stop codons and in the 3' UTR, suggesting a global defect in termination in the absence of eIF5A. Using an in vitro reconstituted translation system, we find that eIF5A strongly promotes the translation of the stalling sequences identified by profiling and increases the rate of peptidyl-tRNA hydrolysis more than 17-fold. We conclude that eIF5A functions broadly in elongation and termination, rationalizing its high cellular abundance and essential nature.

LanguageEnglish (US)
Pages194-205.e5
JournalMolecular Cell
Volume66
Issue number2
DOIs
StatePublished - Apr 20 2017

Fingerprint

Ribosomes
Proline
In Vitro Techniques
Peptide Initiation Factors
Terminator Codon
3' Untranslated Regions
Biochemistry
Hydrolysis
peptidyl-tRNA

Keywords

  • biochemistry
  • eIF5A
  • ribosome profiling
  • translation elongation
  • translation termination

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Schuller, A. P., Wu, C. C. C., Dever, T. E., Buskirk, A. R., & Green, R. (2017). eIF5A Functions Globally in Translation Elongation and Termination. Molecular Cell, 66(2), 194-205.e5. DOI: 10.1016/j.molcel.2017.03.003

eIF5A Functions Globally in Translation Elongation and Termination. / Schuller, Anthony P.; Wu, Colin Chih Chien; Dever, Thomas E.; Buskirk, Allen R.; Green, Rachel.

In: Molecular Cell, Vol. 66, No. 2, 20.04.2017, p. 194-205.e5.

Research output: Research - peer-reviewArticle

Schuller, AP, Wu, CCC, Dever, TE, Buskirk, AR & Green, R 2017, 'eIF5A Functions Globally in Translation Elongation and Termination' Molecular Cell, vol 66, no. 2, pp. 194-205.e5. DOI: 10.1016/j.molcel.2017.03.003
Schuller AP, Wu CCC, Dever TE, Buskirk AR, Green R. eIF5A Functions Globally in Translation Elongation and Termination. Molecular Cell. 2017 Apr 20;66(2):194-205.e5. Available from, DOI: 10.1016/j.molcel.2017.03.003
Schuller, Anthony P. ; Wu, Colin Chih Chien ; Dever, Thomas E. ; Buskirk, Allen R. ; Green, Rachel. / eIF5A Functions Globally in Translation Elongation and Termination. In: Molecular Cell. 2017 ; Vol. 66, No. 2. pp. 194-205.e5
@article{70c5e26c251f404684e0f3debeee1c96,
title = "eIF5A Functions Globally in Translation Elongation and Termination",
abstract = "The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches. Our data also show ribosome accumulation at stop codons and in the 3' UTR, suggesting a global defect in termination in the absence of eIF5A. Using an in vitro reconstituted translation system, we find that eIF5A strongly promotes the translation of the stalling sequences identified by profiling and increases the rate of peptidyl-tRNA hydrolysis more than 17-fold. We conclude that eIF5A functions broadly in elongation and termination, rationalizing its high cellular abundance and essential nature.",
keywords = "biochemistry, eIF5A, ribosome profiling, translation elongation, translation termination",
author = "Schuller, {Anthony P.} and Wu, {Colin Chih Chien} and Dever, {Thomas E.} and Buskirk, {Allen R.} and Rachel Green",
year = "2017",
month = "4",
doi = "10.1016/j.molcel.2017.03.003",
volume = "66",
pages = "194--205.e5",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - eIF5A Functions Globally in Translation Elongation and Termination

AU - Schuller,Anthony P.

AU - Wu,Colin Chih Chien

AU - Dever,Thomas E.

AU - Buskirk,Allen R.

AU - Green,Rachel

PY - 2017/4/20

Y1 - 2017/4/20

N2 - The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches. Our data also show ribosome accumulation at stop codons and in the 3' UTR, suggesting a global defect in termination in the absence of eIF5A. Using an in vitro reconstituted translation system, we find that eIF5A strongly promotes the translation of the stalling sequences identified by profiling and increases the rate of peptidyl-tRNA hydrolysis more than 17-fold. We conclude that eIF5A functions broadly in elongation and termination, rationalizing its high cellular abundance and essential nature.

AB - The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches. Our data also show ribosome accumulation at stop codons and in the 3' UTR, suggesting a global defect in termination in the absence of eIF5A. Using an in vitro reconstituted translation system, we find that eIF5A strongly promotes the translation of the stalling sequences identified by profiling and increases the rate of peptidyl-tRNA hydrolysis more than 17-fold. We conclude that eIF5A functions broadly in elongation and termination, rationalizing its high cellular abundance and essential nature.

KW - biochemistry

KW - eIF5A

KW - ribosome profiling

KW - translation elongation

KW - translation termination

UR - http://www.scopus.com/inward/record.url?scp=85017190109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017190109&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2017.03.003

DO - 10.1016/j.molcel.2017.03.003

M3 - Article

VL - 66

SP - 194-205.e5

JO - Molecular Cell

T2 - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -