Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells

Abstract The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the...

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Autores principales:	Sibylle Schleich, Julieta M. Acevedo, Katharina Clemm von Hohenberg, Aurelio A. Teleman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69183d83402344d889beea0fb8e0e47d
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spelling	oai:doaj.org-article:69183d83402344d889beea0fb8e0e47d2021-12-02T16:06:26ZIdentification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells10.1038/s41598-017-03949-62045-2322https://doaj.org/article/69183d83402344d889beea0fb8e0e47d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03949-6https://doaj.org/toc/2045-2322Abstract The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the medical relevance of DENR and MCTS1, it is worthwhile identifying the transcripts in human cells that depend on DENR and MCTS1 for their translation. We show here that in humans, as in Drosophila, transcripts with short stuORFs require DENR and MCTS1 for their optimal expression. In contrast to Drosophila, however, the dependence on stuORF length in human cells is very strong, so that only transcripts with very short stuORFs coding for 1 amino acid are dependent on DENR and MCTS1. This identifies circa 100 genes as putative DENR and MCTS1 translational targets. These genes are enriched for neuronal genes and G protein-coupled receptors. The identification of DENR and MCTS1 target transcripts will serve as a basis for future studies aimed at understanding the mechanistic involvement of DENR and MCTS1 in cancer and autism.Sibylle SchleichJulieta M. AcevedoKatharina Clemm von HohenbergAurelio A. TelemanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sibylle Schleich Julieta M. Acevedo Katharina Clemm von Hohenberg Aurelio A. Teleman Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
description	Abstract The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the medical relevance of DENR and MCTS1, it is worthwhile identifying the transcripts in human cells that depend on DENR and MCTS1 for their translation. We show here that in humans, as in Drosophila, transcripts with short stuORFs require DENR and MCTS1 for their optimal expression. In contrast to Drosophila, however, the dependence on stuORF length in human cells is very strong, so that only transcripts with very short stuORFs coding for 1 amino acid are dependent on DENR and MCTS1. This identifies circa 100 genes as putative DENR and MCTS1 translational targets. These genes are enriched for neuronal genes and G protein-coupled receptors. The identification of DENR and MCTS1 target transcripts will serve as a basis for future studies aimed at understanding the mechanistic involvement of DENR and MCTS1 in cancer and autism.
format	article
author	Sibylle Schleich Julieta M. Acevedo Katharina Clemm von Hohenberg Aurelio A. Teleman
author_facet	Sibylle Schleich Julieta M. Acevedo Katharina Clemm von Hohenberg Aurelio A. Teleman
author_sort	Sibylle Schleich
title	Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
title_short	Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
title_full	Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
title_fullStr	Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
title_full_unstemmed	Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells
title_sort	identification of transcripts with short stuorfs as targets for denr•mcts1-dependent translation in human cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/69183d83402344d889beea0fb8e0e47d
work_keys_str_mv	AT sibylleschleich identificationoftranscriptswithshortstuorfsastargetsfordenrmcts1dependenttranslationinhumancells AT julietamacevedo identificationoftranscriptswithshortstuorfsastargetsfordenrmcts1dependenttranslationinhumancells AT katharinaclemmvonhohenberg identificationoftranscriptswithshortstuorfsastargetsfordenrmcts1dependenttranslationinhumancells AT aurelioateleman identificationoftranscriptswithshortstuorfsastargetsfordenrmcts1dependenttranslationinhumancells
_version_	1718384965558730752

Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells

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