Skip to main content Accessibility help
×
Home
RNA RNA

Article contents

The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure

Published online by Cambridge University Press:  07 March 2001


YURI V. SVITKIN
Affiliation:
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
ARNIM PAUSE
Affiliation:
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada Present address: Bio-Mega Research Division Boehringer Ingelheim Canada, Laval, Quebec H7S 2G5, Canada.
ASHKAN HAGHIGHAT
Affiliation:
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada Present address: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.
STÉPHANE PYRONNET
Affiliation:
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
GARY WITHERELL
Affiliation:
Questcor Pharmaceuticals, Inc., Hayward, California 94545, USA
GRAHAM J. BELSHAM
Affiliation:
BBSRC Institute for Animal Health, Pirbright, Woking, Surrey GU24 ONF, United Kingdom
NAHUM SONENBERG
Affiliation:
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada

Get access

Abstract

Eukaryotic initiation factor (eIF) 4A functions as a subunit of the initiation factor complex eIF4F, which mediates the binding of mRNA to the ribosome. eIF4A possesses ATPase and RNA helicase activities and is the prototype for a large family of putative RNA helicases (the DEAD box family). It is thought that the function of eIF4A during translation initiation is to unwind the mRNA secondary structure in the 5′ UTR to facilitate ribosome binding. However, the evidence to support this hypothesis is rather indirect, and it was reported that eIF4A is also required for the translation of mRNAs possessing minimal 5′ UTR secondary structure. Were this hypothesis correct, the requirement for eIF4A should correlate with the degree of mRNA secondary structure. To test this hypothesis, the effect of a dominant-negative mutant of mammalian eIF4A on translation of mRNAs with various degrees of secondary structure was studied in vitro. Here, we show that mRNAs containing stable secondary structure in the 5′ untranslated region are more susceptible to inhibition by the eIF4A mutant. The mutant protein also strongly inhibits translation from several picornavirus internal ribosome entry sites (IRES), although to different extents. UV crosslinking of eIF4F subunits and eIF4B to the mRNA cap structure is dramatically reduced by the eIF4A mutant and RNA secondary structure. Finally, the eIF4A mutant forms a more stable complex with eIF4G, as compared to the wild-type eIF4A, thus explaining the mechanism by which substoichiometric amounts of mutant eIF4A inhibit translation.


Type
Research Article
Information
Copyright
© 2001 RNA Society

Access options

Get access to the full version of this content by using one of the access options below.

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 3
Total number of PDF views: 48 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 2nd December 2020. This data will be updated every 24 hours.

Hostname: page-component-79f79cbf67-fnl7t Total loading time: 1.417 Render date: 2020-12-02T19:41:43.763Z Query parameters: { "hasAccess": "0", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags last update: Wed Dec 02 2020 19:06:45 GMT+0000 (Coordinated Universal Time) Feature Flags: { "metrics": true, "metricsAbstractViews": false, "peerReview": true, "crossMark": true, "comments": true, "relatedCommentaries": true, "subject": true, "clr": false, "languageSwitch": true }

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *