{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:27:39Z","timestamp":1785792459816,"version":"3.56.0"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,7,11]]},"abstract":"<jats:p>Long noncoding RNAs (lncRNAs) are important regulators of skeletal muscle physiology, with altered expression noted in several human diseases including type 2 diabetes. We report that TMEM9B-AS1, a previously uncharacterized lncRNA, is down-regulated in skeletal muscle of men with type 2 diabetes and skeletal muscle from individuals with sarcopenia. Silencing of TMEM9B-AS1 in primary human myotubes attenuated protein synthesis, concomitant with reduced phosphorylation of ribosomal protein S6. Moreover, we show that TMEM9B-AS1 plays a pivotal role in regulation of ribosomal biogenesis by facilitating messenger RNA stabilization of the transcription factor MYC through direct physical interaction with the RNA binding protein, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Disrupted ribosomal biogenesis resulting from TMEM9B-AS1 silencing leads to decreased expression of muscle contractile and structural proteins important for maintenance of skeletal muscle mass and function. Collectively, our data reveal a role of TMEM9B-AS1 in skeletal muscle loss associated with metabolic disorders.<\/jats:p>","DOI":"10.1126\/sciadv.ads4371","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T17:58:57Z","timestamp":1752083937000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Down-regulation of human-specific lncRNA TMEM9B-AS1 in skeletal muscle of people with type 2 diabetes affects ribosomal biogenesis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-4479","authenticated-orcid":true,"given":"Ilke","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden."},{"name":"Faculty of Medicine, Mondor Institute for Biomedical Research, INSERM U955, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2452-1655","authenticated-orcid":true,"given":"Jonathon A. B.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Caria","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-3808","authenticated-orcid":true,"given":"Iurii","family":"Orlov","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Mondor Institute for Biomedical Research, INSERM U955, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9708-0750","authenticated-orcid":true,"given":"Mladen","family":"Savikj","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5771","authenticated-orcid":true,"given":"Aidan J.","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-5960","authenticated-orcid":true,"given":"Kristian","family":"Lian","sequence":"additional","affiliation":[{"name":"Section for Health and Exercise Physiology, Department of Public Health and Sport Sciences, Inland Norway University of Applied Sciences, Lillehammer, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-2018","authenticated-orcid":true,"given":"Stian","family":"Ellefsen","sequence":"additional","affiliation":[{"name":"Section for Health and Exercise Physiology, Department of Public Health and Sport Sciences, Inland Norway University of Applied Sciences, Lillehammer, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-7497","authenticated-orcid":true,"given":"Juleen R.","family":"Zierath","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden."},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-0258","authenticated-orcid":true,"given":"Anna","family":"Krook","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.132159.111"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0311-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00457"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14370"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2013.02.006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15728"},{"key":"e_1_3_2_9_2","first-page":"785","article-title":"Muscle matters: The effects of medically induced weight loss on skeletal muscle","volume":"12","author":"Prado C. M.","year":"2024","unstructured":"C. M. Prado, S. M. Phillips, M. C. Gonzalez, S. B. Heymsfield, Muscle matters: The effects of medically induced weight loss on skeletal muscle. Lancet. 12, 785\u2013787 (2024).","journal-title":"Lancet."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.6586"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.05.009"},{"key":"e_1_3_2_12_2","first-page":"30","article-title":"Regulation of ribosome biogenesis in skeletal muscle hypertrophy","volume":"34","author":"Figueiredo V. C.","year":"2019","unstructured":"V. C. Figueiredo, J. J. McCarthy, Regulation of ribosome biogenesis in skeletal muscle hypertrophy. Phys. Ther. 34, 30\u201342 (2019).","journal-title":"Phys. Ther."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12636"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01285-4"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00963.2018"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00164.2021"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo3192"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi9654"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2013.182"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.039"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20123-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26427-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2672"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2819"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700906200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1362"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.606"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.12.3959-3969.2002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4765-z"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1248"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.287540.116"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.1175909"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1142"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109912"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.22.7046"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2999973"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-2537"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0264"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000082"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.1.C120"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041539"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13806"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-024-05446-x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13694-1"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005618"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00866-6"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.10.004"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2020.05.007"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-01799-x"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.03.001"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0045-z"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP272857"},{"key":"e_1_3_2_55_2","first-page":"RP89001","article-title":"Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression","volume":"12","author":"Lin J.","year":"2023","unstructured":"J. Lin, Y. Wen, J. Tang, X. Zhang, H. Zhang, H. Zhu, Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression. eLife 12, RP89001 (2023).","journal-title":"eLife"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2004.01259.x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1314"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13182"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh2169"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254917"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1858"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02664-20"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.ads4371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T17:59:55Z","timestamp":1752083995000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ads4371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":65,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2025,7,11]]}},"alternative-id":["10.1126\/sciadv.ads4371"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.ads4371","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]},"assertion":[{"value":"2024-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eads4371"}}