Publication Date:
2014-07-22
Description:
During cap-dependent eukaryotic translation initiation, ribosomes scan messenger RNA from the 5' end to the first AUG start codon with favourable sequence context. For many mRNAs this AUG belongs to a short upstream open reading frame (uORF), and translation of the main downstream ORF requires re-initiation, an incompletely understood process. Re-initiation is thought to involve the same factors as standard initiation. It is unknown whether any factors specifically affect translation re-initiation without affecting standard cap-dependent translation. Here we uncover the non-canonical initiation factors density regulated protein (DENR) and multiple copies in T-cell lymphoma-1 (MCT-1; also called MCTS1 in humans) as the first selective regulators of eukaryotic re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR-MCT-1 for their proper translation, yielding a novel class of mRNAs that can be co-regulated and that is enriched for regulatory proteins such as oncogenic kinases. Collectively, our data reveal that cells have a previously unappreciated translational control system with a key role in supporting proliferation and tissue growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134322/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schleich, Sibylle -- Strassburger, Katrin -- Janiesch, Philipp Christoph -- Koledachkina, Tatyana -- Miller, Katharine K -- Haneke, Katharina -- Cheng, Yong-Sheng -- Kuchler, Katrin -- Stoecklin, Georg -- Duncan, Kent E -- Teleman, Aurelio A -- 260602/European Research Council/International -- England -- Nature. 2014 Aug 14;512(7513):208-12. doi: 10.1038/nature13401. Epub 2014 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany. ; 1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2]. ; 1] Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany [2]. ; Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany. ; 1] German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Zentrum fur Molekulare Biologie der Universitat Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. ; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043021" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Proliferation
;
Cells, Cultured
;
Drosophila Proteins/genetics/*metabolism
;
Drosophila melanogaster/cytology/genetics/growth & development
;
Eukaryotic Initiation Factors/genetics/*metabolism
;
Gene Expression Regulation/*genetics
;
Open Reading Frames
;
Protein Biosynthesis/*genetics
;
Signal Transduction
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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