Mohamed A. El-Brolosy, Atharv Oak, An T. Hoang, Yassine Damergi, André Fischer, Reuben A. Saunders, Jingchuan Luo, Amer Balabaki, Jeremy Guez, Troy W. Whitfield, Seth R. Goldman, Arash Latifkar, Yuancheng Ryan Lu, Didier Y. R. Stainier, Konrad J. Karczewski, Olivia Corradin, Jonathan S. Weissman
Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmically generated mRNA fragments affect nuclear transcription remains poorly understood. Using genome-wide CRISPR screens, we uncover ILF3 as an RNA binding protein connecting cytoplasmic mRNA decay and transcription during TA and show that it is required for a range of TA substrates. ILF3 is enriched at adapting genes’ RNAs, and its artificial recruitment through dCas13 promotes gene expression. Using tiling oligonucleotide screens, we identify trigger RNA fragments that activate adapting genes when introduced into cells. Further functional dissection reveals a critical role for homology between trigger and target sequences. These findings enhance our molecular understanding of TA and inform the design of programmable oligonucleotides for gene expression augmentation.
{"title":"Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation","authors":"Mohamed A. El-Brolosy, Atharv Oak, An T. Hoang, Yassine Damergi, André Fischer, Reuben A. Saunders, Jingchuan Luo, Amer Balabaki, Jeremy Guez, Troy W. Whitfield, Seth R. Goldman, Arash Latifkar, Yuancheng Ryan Lu, Didier Y. R. Stainier, Konrad J. Karczewski, Olivia Corradin, Jonathan S. Weissman","doi":"10.1126/science.aea1272","DOIUrl":"10.1126/science.aea1272","url":null,"abstract":"<div >Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmically generated mRNA fragments affect nuclear transcription remains poorly understood. Using genome-wide CRISPR screens, we uncover ILF3 as an RNA binding protein connecting cytoplasmic mRNA decay and transcription during TA and show that it is required for a range of TA substrates. ILF3 is enriched at adapting genes’ RNAs, and its artificial recruitment through dCas13 promotes gene expression. Using tiling oligonucleotide screens, we identify trigger RNA fragments that activate adapting genes when introduced into cells. Further functional dissection reveals a critical role for homology between trigger and target sequences. These findings enhance our molecular understanding of TA and inform the design of programmable oligonucleotides for gene expression augmentation.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew K. Schulz, Lena V. Kaufmann, Lawrence T. Smith, Deepti S. Philip, Hilda David, Jelena Lazovic, Michael Brecht, Gunther Richter, Katherine J. Kuchenbecker
Keratin composites enable animals to hike with hooves, fly with feathers, and sense with skin. Mammalian whiskers are elongated keratin rods attached to tactile skin structures that extend the animal’s sensory volume. We investigated the whiskers that cover Asian elephant (Elephas maximus) trunks and found that they are geometrically and mechanically tailored to facilitate tactile perception by encoding contact location in the amplitude and frequency of the vibrotactile signal felt at the whisker base. Elephant whiskers emerge from armored trunk skin and shift from a thick, circular, porous, stiff base to a thin, ovular, dense, soft tip. These functional gradients of geometry, porosity, and stiffness independently tune the neuromechanics of elephant trunk touch to facilitate highly dexterous manipulation while ensuring whisker durability.
{"title":"Functional gradients facilitate tactile sensing in elephant whiskers","authors":"Andrew K. Schulz, Lena V. Kaufmann, Lawrence T. Smith, Deepti S. Philip, Hilda David, Jelena Lazovic, Michael Brecht, Gunther Richter, Katherine J. Kuchenbecker","doi":"10.1126/science.adx8981","DOIUrl":"10.1126/science.adx8981","url":null,"abstract":"<div >Keratin composites enable animals to hike with hooves, fly with feathers, and sense with skin. Mammalian whiskers are elongated keratin rods attached to tactile skin structures that extend the animal’s sensory volume. We investigated the whiskers that cover Asian elephant (<i>Elephas maximus</i>) trunks and found that they are geometrically and mechanically tailored to facilitate tactile perception by encoding contact location in the amplitude and frequency of the vibrotactile signal felt at the whisker base. Elephant whiskers emerge from armored trunk skin and shift from a thick, circular, porous, stiff base to a thin, ovular, dense, soft tip. These functional gradients of geometry, porosity, and stiffness independently tune the neuromechanics of elephant trunk touch to facilitate highly dexterous manipulation while ensuring whisker durability.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bianca Lopez, Marc S. Lavine, Joana Osório, Yevgeniya Nusinovich, Corinne Simonti, Keith T. Smith, Yury Suleymanov
{"title":"In Other Journals","authors":"Bianca Lopez, Marc S. Lavine, Joana Osório, Yevgeniya Nusinovich, Corinne Simonti, Keith T. Smith, Yury Suleymanov","doi":"10.1126/science.aeg3197","DOIUrl":"10.1126/science.aeg3197","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Taking a sharp turn","authors":"Theresa A. Maldonado","doi":"10.1126/science.aeg1977","DOIUrl":"10.1126/science.aeg1977","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum for the Research Article “WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring”","authors":"","doi":"10.1126/science.aeg0713","DOIUrl":"10.1126/science.aeg0713","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stewarding AI in agriculture research","authors":"Ismahane Elouafi","doi":"10.1126/science.aef0964","DOIUrl":"10.1126/science.aef0964","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
More than half of canines trained to help people with disabilities fail to graduate. Can science help?
超过一半的训练帮助残疾人的狗没有毕业。科学能帮上忙吗？
{"title":"Building a better working dog.","authors":"David Grimm","doi":"10.1126/science.aeg3195","DOIUrl":"https://doi.org/10.1126/science.aeg3195","url":null,"abstract":"<p><p>More than half of canines trained to help people with disabilities fail to graduate. Can science help?</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":"650-653"},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiang Zhang, Huamin Li, Peiping Yu, Pengyu Liu, Ning Sun, Yiyan Wang, Chunlai Tu, Yiping Liu, Yan Wang, Xinyang Yue, Linlin Ma, Wen Wen, Jinyang Xu, Zhaofeng Liang, Jingyuan Ma, Fei Song, Zheng Liang, Hao Sun, Daishun Ling, Hongyan Liang, Feng Liu, Yongfeng Hu, Tao Cheng, Jun Li
Electrochemical lithium (Li)–mediated nitrogen (N2) reduction could enable production of ammonia (NH3) at ambient temperatures and pressures, offering a route to reduce carbon emissions in the chemical sector. However, NH3 productivity is often limited by sluggish Li-ion desolvation and diffusion at the solid electrolyte interphase (SEI). Here, we present a concerted desolvation:diffusion layered SEI architecture that provides abundant Li-ion flux for efficient N2 conversion toward NH3 production at high current densities. The SEI comprises stacked inorganic layers with low ion-binding affinity and high ion-conductivity functionalities that increase Li-ion flux by two orders of magnitude. This design strategy achieved N2 electroreduction in a 2 M lithium difluoro(oxalato)borate electrolyte with a Faradaic efficiency of 98% and an energy efficiency of 21% for NH3 production at 100 milliamperes per square centimeter (mA cm−2). The system sustained an 80% Faradaic efficiency over 40 hours, after which performance declined.
电化学锂（Li）介导的氮（N2）还原可以在环境温度和压力下生产氨（NH3），为减少化学行业的碳排放提供了一条途径。然而，NH3的生产效率往往受到锂离子在固体电解质界面（SEI）缓慢的溶解和扩散的限制。在这里，我们提出了一种协调的脱溶：扩散层状SEI结构，它提供了丰富的锂离子通量，在高电流密度下有效地将N2转化为NH3。SEI包括堆叠的无机层，具有低离子结合亲和力和高离子电导率功能，可将锂离子通量提高两个数量级。该设计策略在2 M二氟锂（草酸）硼酸盐电解质中实现了N2电还原，法拉第效率为98%，在100毫安/平方厘米（mA cm - 2）下产生NH3的能量效率为21%。该系统在40小时内保持了80%的法拉第效率，之后性能下降。
{"title":"Enhanced Li-ion diffusion improves N2-to-NH3 current efficiency at 100 mA cm−2","authors":"Qiang Zhang, Huamin Li, Peiping Yu, Pengyu Liu, Ning Sun, Yiyan Wang, Chunlai Tu, Yiping Liu, Yan Wang, Xinyang Yue, Linlin Ma, Wen Wen, Jinyang Xu, Zhaofeng Liang, Jingyuan Ma, Fei Song, Zheng Liang, Hao Sun, Daishun Ling, Hongyan Liang, Feng Liu, Yongfeng Hu, Tao Cheng, Jun Li","doi":"10.1126/science.adw5462","DOIUrl":"10.1126/science.adw5462","url":null,"abstract":"<div >Electrochemical lithium (Li)–mediated nitrogen (N<sub>2</sub>) reduction could enable production of ammonia (NH<sub>3</sub>) at ambient temperatures and pressures, offering a route to reduce carbon emissions in the chemical sector. However, NH<sub>3</sub> productivity is often limited by sluggish Li-ion desolvation and diffusion at the solid electrolyte interphase (SEI). Here, we present a concerted desolvation:diffusion layered SEI architecture that provides abundant Li-ion flux for efficient N<sub>2</sub> conversion toward NH<sub>3</sub> production at high current densities. The SEI comprises stacked inorganic layers with low ion-binding affinity and high ion-conductivity functionalities that increase Li-ion flux by two orders of magnitude. This design strategy achieved N<sub>2</sub> electroreduction in a 2 M lithium difluoro(oxalato)borate electrolyte with a Faradaic efficiency of 98% and an energy efficiency of 21% for NH<sub>3</sub> production at 100 milliamperes per square centimeter (mA cm<sup>−2</sup>). The system sustained an 80% Faradaic efficiency over 40 hours, after which performance declined.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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