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Schleich, S., Strassburger, K., Janiesch, P.C., Koledachkina, T., Miller, K.K., Haneke, K., Cheng, Y.S., Küchler, K., Stoecklin, G., Duncan, K.E., Teleman, A.A. (2014). DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth.  Nature 512(7513): 208--212.
FlyBase ID
FBrf0226143
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC4134322 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Comments on S2 cell line used, Duncan, Teleman.
Duncan and Teleman, 2016.4.25, Comments on S2 cell line used, Duncan, Teleman. [FBrf0232272]

Note

Translation. DENR-MCT1 reinitiates translation.
Zlotorynski, 2014, Nat. Rev. Mol. Cell Biol. 15(8): 498 [FBrf0226351]

Mixed messages: Re-initiation factors regulate translation of animal mRNAs.
Obermayer and Rajewsky, 2014, Cell Res. 24(12): 1383--1384 [FBrf0228476]

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nature
    Title
    Nature
    Publication Year
    1869-
    ISBN/ISSN
    0028-0836
    Data From Reference
    Alleles (8)
    Gene Groups (1)
    Genes (25)
    Physical Interactions (8)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (7)