Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs

Summary: The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements...

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Main Authors: Margaret Rose Davis, Mildred Delaleau, Katherine L.B. Borden
Format: Article
Language:English
Published: Elsevier 2019-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719304632
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author Margaret Rose Davis
Mildred Delaleau
Katherine L.B. Borden
author_facet Margaret Rose Davis
Mildred Delaleau
Katherine L.B. Borden
author_sort Margaret Rose Davis
collection DOAJ
description Summary: The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements of the 3′-end core cleavage complex involved in cleavage and polyadenylation (CPA), including CPSF3, the enzyme responsible for cleavage, as well as its co-factors CPSF1, CPSF2, CPSF4, Symplekin, WDR33, and FIP1L1. Using multiple strategies, we demonstrate that eIF4E stimulates 3′-end cleavage of selected RNAs. eIF4E physically interacts with CPSF3, CPSF1, and uncleaved target RNA, suggesting it acts directly and indirectly on the pathway. Through these effects, eIF4E can generate better substrates for its mRNA export and translation activities. Thus, we identified an unanticipated function for eIF4E in 3′-end processing of specific target RNAs, and this function could potentially affect the expression of a broad range of oncoproteins. : Davis et al. demonstrate that the eukaryotic translation initiation factor eIF4E, which is usually associated with nuclear export and translation of specific transcripts, also acts in 3′-end processing of selected RNAs. Through these effects, eIF4E can generate better substrates for its export and translation activities and, thus, modulate the proteome. Keywords: nuclear RNA export, polyadenylation, translation
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spelling doaj.art-48357669f435479387bb7fc6d5bf602e2022-12-21T18:13:28ZengElsevierCell Reports2211-12472019-04-0127513971408.e4Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAsMargaret Rose Davis0Mildred Delaleau1Katherine L.B. Borden2Institute of Research in Immunology and Cancer (IRIC), Department of Pathology and Cell Biology, Université de Montréal, Pavillon Marcelle-Coutu, 2950 Chemin de Polytechnique, Montreal, QC H3T 1J4, CanadaInstitute of Research in Immunology and Cancer (IRIC), Department of Pathology and Cell Biology, Université de Montréal, Pavillon Marcelle-Coutu, 2950 Chemin de Polytechnique, Montreal, QC H3T 1J4, CanadaInstitute of Research in Immunology and Cancer (IRIC), Department of Pathology and Cell Biology, Université de Montréal, Pavillon Marcelle-Coutu, 2950 Chemin de Polytechnique, Montreal, QC H3T 1J4, Canada; Corresponding authorSummary: The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements of the 3′-end core cleavage complex involved in cleavage and polyadenylation (CPA), including CPSF3, the enzyme responsible for cleavage, as well as its co-factors CPSF1, CPSF2, CPSF4, Symplekin, WDR33, and FIP1L1. Using multiple strategies, we demonstrate that eIF4E stimulates 3′-end cleavage of selected RNAs. eIF4E physically interacts with CPSF3, CPSF1, and uncleaved target RNA, suggesting it acts directly and indirectly on the pathway. Through these effects, eIF4E can generate better substrates for its mRNA export and translation activities. Thus, we identified an unanticipated function for eIF4E in 3′-end processing of specific target RNAs, and this function could potentially affect the expression of a broad range of oncoproteins. : Davis et al. demonstrate that the eukaryotic translation initiation factor eIF4E, which is usually associated with nuclear export and translation of specific transcripts, also acts in 3′-end processing of selected RNAs. Through these effects, eIF4E can generate better substrates for its export and translation activities and, thus, modulate the proteome. Keywords: nuclear RNA export, polyadenylation, translationhttp://www.sciencedirect.com/science/article/pii/S2211124719304632
spellingShingle Margaret Rose Davis
Mildred Delaleau
Katherine L.B. Borden
Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
Cell Reports
title Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
title_full Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
title_fullStr Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
title_full_unstemmed Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
title_short Nuclear eIF4E Stimulates 3′-End Cleavage of Target RNAs
title_sort nuclear eif4e stimulates 3 end cleavage of target rnas
url http://www.sciencedirect.com/science/article/pii/S2211124719304632
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AT mildreddelaleau nucleareif4estimulates3endcleavageoftargetrnas
AT katherinelbborden nucleareif4estimulates3endcleavageoftargetrnas