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}
Edoardo Gianni, Samantha L Y Kwok, Christopher J K Wan, Kevin Goeij, Bryce E Clifton, Enrico S Colizzi, James Attwater, Philipp Holliger
The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence. Here we describe QT45: a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice. QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days. The discovery of polymerase activity in a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.
{"title":"A small polymerase ribozyme that can synthesize itself and its complementary strand.","authors":"Edoardo Gianni, Samantha L Y Kwok, Christopher J K Wan, Kevin Goeij, Bryce E Clifton, Enrico S Colizzi, James Attwater, Philipp Holliger","doi":"10.1126/science.adt2760","DOIUrl":"https://doi.org/10.1126/science.adt2760","url":null,"abstract":"<p><p>The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence. Here we describe QT45: a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice. QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days. The discovery of polymerase activity in a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":" ","pages":"eadt2760"},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182107","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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