{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:48:07Z","timestamp":1765878487500,"version":"3.48.0"},"reference-count":55,"publisher":"Portland Press Ltd.","issue":"04","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:p>High frequency of lysogenization X (HflX) is an enigmatic protein that has been implicated in rescuing translationally stalled ribosomes and macrolide-lincosamide antibiotic resistance, as well as in ribosome biogenesis. The protein shows significant sequence and structural variation across species, including variation among paralogs within the same organism. Recent cryo-EM structure determination of ribosome-HflX complexes from different eubacterial species has provided important mechanistic clues to HflX function. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared with their eubacterial homologs, suggesting that the mycobacterial HflX could have distinct functional mechanisms. This article presents a brief overview of these studies highlighting (i) what we have learned from recent multiple mycobacterial ribosome-HflX complex structures and (ii) the roles of mycobacteria-specific segments in ribosomal RNA disordering that leads to ribosome splitting to rescue translation by removing the drug-bound stalled ribosome from the translationally active polysome pool. Future studies needed to resolve some of the outstanding issues related to HflX function and dynamics are also discussed.<\/jats:p>","DOI":"10.1042\/bst20253084","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:56:01Z","timestamp":1755694561000},"page":"1067-1075","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance"],"prefix":"10.1042","volume":"53","author":[{"given":"Soneya","family":"Majumdar","sequence":"first","affiliation":[{"name":"1Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY, 12237, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pallavi","family":"Ghosh","sequence":"additional","affiliation":[{"name":"2Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, NY 12237, U.S.A."},{"name":"3Department of Biomedical Sciences, University at Albany, Albany, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-0065","authenticated-orcid":false,"given":"Rajendra K.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"1Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY, 12237, U.S.A."},{"name":"3Department of Biomedical Sciences, University at Albany, Albany, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"2025121604430707100_BST-2025-3084C1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0300-9084(97)86718-1","article-title":"Dual functions of ribosome recycling factor in protein biosynthesis: disassembling the termination complex and preventing translational errors","volume":"78","author":"Janosi","year":"1996","journal-title":"Biochimie"},{"key":"2025121604430707100_BST-2025-3084C2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0092-8674(02)00938-8","article-title":"Orientation of ribosome recycling factor in the ribosome from directed hydroxyl radical probing","volume":"111","author":"Lancaster","year":"2002","journal-title":"Cell"},{"key":"2025121604430707100_BST-2025-3084C3","doi-asserted-by":"crossref","first-page":"8900","DOI":"10.1073\/pnas.0401904101","article-title":"Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: Functional implications","volume":"101","author":"Agrawal","year":"2004","journal-title":"Proc. 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