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Meydan, S.* ; Marks, J.* ; Klepacki, D.* ; Sharma, V. ; Baranov, P.V.* ; Firth, A.E.* ; Margus, T.* ; Kefi, A.* ; Vázquez-Laslop, N.* ; Mankin, A.S.*

Retapamulin-assisted ribosome profiling reveals the alternative bacterial proteome.

Mol. Cell 74, 481-493.e6 (2019)
Verlagsversion Preprint Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The use of alternative translation initiation sites enables production of more than one protein from a single gene, thereby expanding the cellular proteome. Although several such examples have been serendipitously found in bacteria, genome-wide mapping of alternative translation start sites has been unattainable. We found that the antibiotic retapamulin specifically arrests initiating ribosomes at start codons of the genes. Retapamulin-enhanced Ribo-seq analysis (Ribo-RET) not only allowed mapping of conventional initiation sites at the beginning of the genes, but strikingly, it also revealed putative internal start sites in a number of Escherichia coli genes. Experiments demonstrated that the internal start codons can be recognized by the ribosomes and direct translation initiation in vitro and in vivo. Proteins, whose synthesis is initiated at internal in-frame and out-of-frame start sites, can be functionally important and contribute to the "alternative" bacterial proteome. The internal start sites may also play regulatory roles in gene expression.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Alternative Initiation ; Arcb ; Internal Genes ; Retapamulin ; Ribosome Profiling ; Rpn ; Spea ; Translation Initiation; Biosynthetic Arginine Decarboxylase; Translational Initiation Sites; Escherichia-coli; Wide Analysis; Start Sites; In-vivo; Gene; Identification; Pleuromutilin; Proteins
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Zeitschrift Molecular Cell
Quellenangaben Band: 74, Heft: 3, Seiten: 481-493.e6 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)