@article{68040450feff47c4b7bb2646a289d16a,
title = "Decoding the Function of Expansion Segments in Ribosomes",
abstract = "Expansion segments (ESs) are enigmatic insertions within the eukaryotic ribosome, the longest of which resemble tentacle-like extensions that vary in length and sequence across evolution, with a largely unknown function. By selectively engineering rRNA in yeast, we find that one of the largest ESs, ES27L, has an unexpected function in translation fidelity. Ribosomes harboring a deletion in the distal portion of ES27L have increased amino acid misincorporation, as well as readthrough and frameshifting errors. By employing quantitative mass spectrometry, we further find that ES27L acts as an RNA scaffold to facilitate binding of a conserved enzyme, methionine amino peptidase (MetAP). We show that MetAP unexpectedly controls the accuracy of ribosome decoding, which is coupled to an increase in its enzymatic function through its interaction with ES27L. These findings reveal that variable ESs of the ribosome serve important functional roles and act as platforms for the binding of proteins that modulate translation across evolution.",
keywords = "ES, ES27L, MetAP, expansion segment, methionine amino peptidase, rRNA, ribosome, translation fidelity",
author = "Kotaro Fujii and Susanto, {Teodorus Theo} and Saumya Saurabh and Maria Barna",
note = "Funding Information: We thank the Barna lab members and D. Ruggero for constructive suggestions and thoughtful critiques of the work. We thank E. Craig (University of Wisconsin-Madison) for sharing the Zuo1 antibody and F. Ward from Cate lab (UC Berkeley) for the Rps13/uS13 antibody. We thank K. Asano (Kansas State University), M. Kitabatake (Ohno lab, Kyoto University), and A. Chakravarty (Jarosz lab, Stanford University) for providing yeast strains. We thank T. Inada (Tohoku University), P. Farabough (University of Maryland), and J. Dinman (University of Maryland) for providing plasmid constructs. This work was supported by New York Stem Cell Foundation grant NYSCF-R-I36 (M.B.), NIH grant 1R01HD086634 (M.B.), an Alfred P. Sloan Research Fellowship (M.B.), and a Pew Scholars Award (M.B.). K.F. was supported by the Uehara Memorial Foundation and Human Frontier Science Program Fellowship. T.T.S. was supported by a National Science Scholarship (PhD) from the Agency for Science, Technology and Research . M.B. is a New York Stem Cell Foundation Robertson Investigator. Funding Information: We thank the Barna lab members and D. Ruggero for constructive suggestions and thoughtful critiques of the work. We thank E. Craig (University of Wisconsin-Madison) for sharing the Zuo1 antibody and F. Ward from Cate lab (UC Berkeley) for the Rps13/uS13 antibody. We thank K. Asano (Kansas State University), M. Kitabatake (Ohno lab, Kyoto University), and A. Chakravarty (Jarosz lab, Stanford University) for providing yeast strains. We thank T. Inada (Tohoku University), P. Farabough (University of Maryland), and J. Dinman (University of Maryland) for providing plasmid constructs. This work was supported by New York Stem Cell Foundation grant NYSCF-R-I36 (M.B.), NIH grant 1R01HD086634 (M.B.), an Alfred P. Sloan Research Fellowship (M.B.), and a Pew Scholars Award (M.B.). K.F. was supported by the Uehara Memorial Foundation and Human Frontier Science Program Fellowship. T.T.S. was supported by a National Science Scholarship (PhD) from the Agency for Science, Technology and Research. M.B. is a New York Stem Cell Foundation Robertson Investigator. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = dec,
day = "20",
doi = "10.1016/j.molcel.2018.11.023",
language = "English (US)",
volume = "72",
pages = "1013--1020.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}