@article{f5d01f8b00614aac9cc7d9d0c869ef54,
title = "Negative charge in the RACK1 loop broadens the translational capacity of the human ribosome",
abstract = "Although the roles of initiation factors, RNA binding proteins, and RNA elements in regulating translation are well defined, how the ribosome functionally diversifies remains poorly understood. In their human hosts, poxviruses phosphorylate serine 278 (S278) at the tip of a loop domain in the small subunit ribosomal protein RACK1, thereby mimicking negatively charged residues in the RACK1 loops of dicot plants and protists to stimulate translation of transcripts with 5′ poly(A) leaders. However, how a negatively charged RACK1 loop affects ribosome structure and its broader translational output is not known. Here, we show that although ribotoxin-induced stress signaling and stalling on poly(A) sequences are unaffected, negative charge in the RACK1 loop alters the swivel motion of the 40S head domain in a manner similar to several internal ribosome entry sites (IRESs), confers resistance to various protein synthesis inhibitors, and broadly supports noncanonical modes of translation.",
keywords = "IRES, alternative initiation, cryo-EM, mRNA specification, post-translational modification, protein synthesis, ribosome, selective translation, structure",
author = "Rollins, {Madeline G.} and Manidip Shasmal and Nathan Meade and Helen Astar and Shen, {Peter S.} and Derek Walsh",
note = "Funding Information: We thank the Arnold and Mabel Beckman Center for Cryo-EM and Center for High Performance Computing at the University of Utah for support in data collection and data processing, respectively. This work was supported by grants from the NIH to M.G.R. ( F31 AI152548 ), P.S.S. ( R35 GM133772 ), and D.W. ( R01 AI127456 and Diversity Supplement R01 AI127456-S ). Funding Information: We thank the Arnold and Mabel Beckman Center for Cryo-EM and Center for High Performance Computing at the University of Utah for support in data collection and data processing, respectively. This work was supported by grants from the NIH to M.G.R. (F31 AI152548), P.S.S. (R35 GM133772), and D.W. (R01 AI127456 and Diversity Supplement R01 AI127456-S). M.G.R. generated cell lines and performed the bulk of functional studies, with assistance from N.M. N.M. and H.A. performed and analyzed reporter assays. M.S. isolated ribosomes and analyzed cryo-EM data with P.S.S. P.S.S. and D.W. oversaw the project. M.G.R. drafted the manuscript. P.S.S. and D.W. contributed to editing. All authors reviewed and approved the manuscript. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = sep,
day = "7",
doi = "10.1016/j.celrep.2021.109663",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}