{"date_published":"2026-02-11T00:00:00Z","month":"02","day":"11","abstract":[{"text":"Gene duplication underlies evolutionary innovation, yet many paralogues remain highly similar, raising questions about their functional divergence and physiological relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue SNRPN share over 90% sequence identity, but their distinct expression patterns - SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized functions. Why mammals have two different spliceosomes has remained obscure. Here, we generated isogenic human cell lines expressing ectopically either SNRPB or SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy metabolism and mitochondrial function, leading to increased mitochondrial abundance and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine methylation in its C-terminal region that is sensitive to translation inhibition and amino acid availability. The SNRPN-dependent transcriptome responds to translation inhibition by stabilizing long, intron-rich genes involved in amino acid and energy metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism that differentiates the two paralogues. This suggests that SNRPN functions as a metabolic-specialized spliceosomal subunit thereby providing tissue-specific adaptation of RNA processing in mammals.","lang":"eng"}],"status":"public","OA_type":"green","oa_version":"Preprint","acknowledgement":"We thank Oliver Mühlemann and Alex Hofer (University of Bern) for sharing SMG inhibitors\r\nand for their expertise in nonsense-mediated mRNA decay and Maria Hondele for critical\r\nreading of the manuscript draft. We also thank the IMB Genomics Core Facility for assistance\r\nwith library preparation and sequencing, Martin Möckel and the IMB Protein Production Core\r\nFacility for providing enzymes used in this work, Marton Gelleri together with the IMB\r\nMicroscopy Core Facility for support with microscopy and FRAP experiments, Jasmin Cartano\r\nfor proteomics sample processing and the IMB Flow Cytometry Core Facility for support. In\r\naddition, we thank the Imaging Core Facility (IMCF) and the FACS Core Facility at the\r\nBiozentrum, University of Basel, for technical assistance. CIKV acknowledges funding by the\r\nDeutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Individual Grant\r\nProject no. 513744403, Scientific Network Grant Project no. 531902894, GRK2526 “Genevo”\r\n- Project no. 407023052”, GRK2859 (“4R”) - Project no. 491145305, Forschungsinitiative\r\nRheinland-Pfalz (ReALity), the EMBO Young Investigator Program (5795), institutional\r\nfunding from the Institute of Molecular Biology and funds from the Kanton Basel-Stadt and\r\nBasel-Land provided to the Biozentrum of the University Basel. J.H.G.F.G. was part of the\r\n‘Science of Healthy Ageing Research Programme’ (SHARP) initiative funded by RhinelandPalatinate’s Ministry of Science, Education and Culture. PR is funded by the Biozentrum PhD\r\nFellowships Program. MFB received financial support from the intramural High Potentials\r\nGrant program of the University Medical Center Mainz, Forschungsinitiative Rheinland-Pfalz\r\n(ReALity) and Stiftungen zugunsten der Medizinischen Fakultät der LMU Klinikum (26069).\r\nInstruments in the IMB core facilities were supported by funds from the DFG: Laser Scanning\r\nConfocal (Leica Stellaris 8 Falcon, funded by the DFG - Project #497669232), Orbitrap Astral system (funded by the DFG - Project #524805621) and BD LSRFortessa SOPR is funded by\r\nthe DFG - Project #210253511.\r\n","article_processing_charge":"No","title":"The splicing paralogues SNRPB and SNRPN control differential metabolic states.","citation":{"chicago":"Polat Haas, Feyza, Ana Villalba Requena, Polina Rusina, Anusha Gopalan, Hector Fritz, Azamat Akhmetkaliyev, Frank Ruehle, et al. “The Splicing Paralogues SNRPB and SNRPN Control Differential Metabolic States.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.02.11.705284\">https://doi.org/10.64898/2026.02.11.705284</a>.","ista":"Polat Haas F, Villalba Requena A, Rusina P, Gopalan A, Fritz H, Akhmetkaliyev A, Ruehle F, Einsiedel A, Szczepinska A, Kielisch F, Chen J-X, Nguyen S, Schmidlin T, Hippenmeyer S, Bailicata MF, Keller Valsecchi CI. The splicing paralogues SNRPB and SNRPN control differential metabolic states. bioRxiv, <a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>.","mla":"Polat Haas, Feyza, et al. “The Splicing Paralogues SNRPB and SNRPN Control Differential Metabolic States.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>.","ama":"Polat Haas F, Villalba Requena A, Rusina P, et al. The splicing paralogues SNRPB and SNRPN control differential metabolic states. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>","apa":"Polat Haas, F., Villalba Requena, A., Rusina, P., Gopalan, A., Fritz, H., Akhmetkaliyev, A., … Keller Valsecchi, C. I. (n.d.). The splicing paralogues SNRPB and SNRPN control differential metabolic states. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.02.11.705284\">https://doi.org/10.64898/2026.02.11.705284</a>","short":"F. Polat Haas, A. Villalba Requena, P. Rusina, A. Gopalan, H. Fritz, A. Akhmetkaliyev, F. Ruehle, A. Einsiedel, A. Szczepinska, F. Kielisch, J.-X. Chen, S. Nguyen, T. Schmidlin, S. Hippenmeyer, M.F. Bailicata, C.I. Keller Valsecchi, BioRxiv (n.d.).","ieee":"F. Polat Haas <i>et al.</i>, “The splicing paralogues SNRPB and SNRPN control differential metabolic states.,” <i>bioRxiv</i>. ."},"date_updated":"2026-02-23T11:03:33Z","author":[{"last_name":"Polat Haas","first_name":"Feyza","full_name":"Polat Haas, Feyza"},{"orcid":"0000-0002-5615-5277","full_name":"Villalba Requena, Ana","first_name":"Ana","last_name":"Villalba Requena","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247"},{"full_name":"Rusina, Polina","first_name":"Polina","last_name":"Rusina"},{"last_name":"Gopalan","full_name":"Gopalan, Anusha","first_name":"Anusha"},{"first_name":"Hector","full_name":"Fritz, Hector","last_name":"Fritz"},{"first_name":"Azamat","full_name":"Akhmetkaliyev, Azamat","last_name":"Akhmetkaliyev"},{"full_name":"Ruehle, Frank","first_name":"Frank","last_name":"Ruehle"},{"first_name":"Anna","full_name":"Einsiedel, Anna","last_name":"Einsiedel"},{"full_name":"Szczepinska, Anna","first_name":"Anna","last_name":"Szczepinska"},{"first_name":"Fridolin","full_name":"Kielisch, Fridolin","last_name":"Kielisch"},{"last_name":"Chen","full_name":"Chen, Jia-Xuan","first_name":"Jia-Xuan"},{"last_name":"Nguyen","full_name":"Nguyen, Susanne","first_name":"Susanne"},{"full_name":"Schmidlin, Thierry","first_name":"Thierry","last_name":"Schmidlin"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"},{"full_name":"Bailicata, M. Felicia","first_name":"M. Felicia","last_name":"Bailicata"},{"full_name":"Keller Valsecchi, Claudia Isabelle","first_name":"Claudia Isabelle","last_name":"Keller Valsecchi"}],"type":"preprint","publication_status":"submitted","OA_place":"repository","publication":"bioRxiv","_id":"21290","main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.02.11.705284"}],"language":[{"iso":"eng"}],"department":[{"_id":"SiHi"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2026-02-17T11:35:59Z","doi":"10.64898/2026.02.11.705284","oa":1,"year":"2026"}