Yanhong Zhang, Yingjuan Qian, Jin Zhang, Wensheng Yan, Yong-Sam Jung, Mingyi Chen, Eric Huang, Kent Lloyd, Yuyou Duan, Jian Wang, Gang Liu, Xinbin Chen
{"title":"Corrigendum: Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2","authors":"Yanhong Zhang, Yingjuan Qian, Jin Zhang, Wensheng Yan, Yong-Sam Jung, Mingyi Chen, Eric Huang, Kent Lloyd, Yuyou Duan, Jian Wang, Gang Liu, Xinbin Chen","doi":"10.1101/gad.353221.125","DOIUrl":"https://doi.org/10.1101/gad.353221.125","url":null,"abstract":"<strong>Genes & Development 31:</strong> 1243–1256 (2017)","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"35 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bing Yang, Brian J. Galletta, Rima M. Sakhawala, Nasser M. Rusan, Katherine McJunkin
{"title":"An intrinsically disordered region of Drosha selectively promotes miRNA biogenesis independent of tissue-specific Microprocessor condensates","authors":"Bing Yang, Brian J. Galletta, Rima M. Sakhawala, Nasser M. Rusan, Katherine McJunkin","doi":"10.1101/gad.352815.125","DOIUrl":"https://doi.org/10.1101/gad.352815.125","url":null,"abstract":"Precise control of miRNA biogenesis is of extreme importance, because misregulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first cleavage step in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the N-terminal region of DROSHA is less characterized due to its high intrinsic disorder. Here we demonstrate that Microprocessor forms condensates with properties consistent with liquid–liquid phase separation (LLPS) in select tissues in <em>Caenorhabditis elegans</em>. Although DRSH-1/Drosha recruitment to granules is only partially dependent on its intrinsically disordered regions (IDRs), one of these N-terminal IDRs is crucial for biogenesis of a subset of miRNAs and normal development. A <em>cis</em> region of IDR-dependent miRNAs confers IDR dependence to another miRNA, suggesting that the IDR recognizes sequences or structures in the miRNA primary transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"45 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MEF2C networks in heart tube development","authors":"Hassan Abdulrazzak, Mark Mercola","doi":"10.1101/gad.353315.125","DOIUrl":"https://doi.org/10.1101/gad.353315.125","url":null,"abstract":"Heart formation depends on the finely tuned activity of transcriptional regulators, yet the networks they control are only now being defined. In this issue of <em>Genes & Development</em>, Muncie-Vasik and colleagues (doi:10.1101/gad.352889.125) analyzed the role of MEF2C, which is a key driver of heart formation. By characterizing MEF2C's temporal effects on mRNA profiles and chromatin structure, the investigators computationally reconstructed downstream gene regulatory networks, which turned out to be remarkably specific for the different heart tube segments that form the inflow tract, chambers, and outflow tract. The results comprise an extremely fine-grained view of the network logic of heart formation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"57 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The two faces of MyoD: repressor and activator of gene expression during myogenesis","authors":"Carmen Birchmeier","doi":"10.1101/gad.353232.125","DOIUrl":"https://doi.org/10.1101/gad.353232.125","url":null,"abstract":"MyoD is well known for its ability to reprogram a broad range of cell types into myogenic cells and for its pioneer function in activating the myogenic program during muscle development and regeneration. The basic helix–loop–helix (bHLH) protein achieves this by directly binding to E-boxes in DNA and recruiting proteins like histone acetyltransferases and the SWI/SNF chromatin remodeling complex. Interestingly, Nicoletti and colleagues (doi:10.1101/gad.352708.125) report in this issue of <em>Genes & Development</em> an unexpected finding; namely, that MyoD can also act as a repressor. This repressive activity is E-box-independent, meaning that MyoD can be indirectly recruited to distinct sites in chromatin. Transcription factor motifs enriched at these sites correspond to E2F, NF-Y, and Jun/Fos motifs. The genes that are repressed by this noncanonical MyoD function control nonmyogenic fates and participate in cell cycle regulation as well as proliferation. At such sites, MyoD binding is associated with chromatin compaction and repression of transcription.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"8 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcription quality control at the promoter-proximal checkpoint","authors":"Daniel Blears, Jesper Q. Svejstrup","doi":"10.1101/gad.352973.125","DOIUrl":"https://doi.org/10.1101/gad.352973.125","url":null,"abstract":"Transcription of protein-coding genes by RNA polymerase II involves a characteristic pausing event downstream from transcription start sites. Such promoter-proximal pausing likely represents a transcription checkpoint, which ensures proper assembly of a fully functional RNAPII elongation complex that is capable of transcribing through the chromatin environment, with correctly modified nascent pre-mRNA. Failure to negotiate this promoter-proximal checkpoint results in termination of transcription and removal of RNAPII from the DNA. This review summarizes current knowledge on the mechanisms that regulate promoter-proximal pausing, maturation of the elongation complex, and the decision of whether to license RNAPII for elongation or prematurely terminate transcription.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"11 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raúl Sánchez-Vázquez, Sonia Burgaz García-Oteyza, Rosa Serrano, Juana M. Flores, Paula Martínez, Maria A. Blasco
{"title":"Mice carrying the homologous human shelterin POT1-L259S mutation linked to pulmonary fibrosis show a telomerase deficiency-like phenotype with telomere shortening with increasing mouse generations","authors":"Raúl Sánchez-Vázquez, Sonia Burgaz García-Oteyza, Rosa Serrano, Juana M. Flores, Paula Martínez, Maria A. Blasco","doi":"10.1101/gad.352855.125","DOIUrl":"https://doi.org/10.1101/gad.352855.125","url":null,"abstract":"Pulmonary fibrosis is a lethal disease associated with damaging insults to the lung and with organismal aging. The presence of short and dysfunctional telomeres has been placed at the origin of this disease in a percentage of both familial and sporadic cases. Recently, a mutation in the telomere-binding protein <em>protection of telomeres 1</em> in humans (<em>hPOT1</em>), the <em>hPOT1 L259S</em> mutation, was found in families with idiopathic pulmonary fibrosis. Here, we generated a <em>Pot1a</em><sup><em>L261S</em></sup> knock-in mouse harboring the murine homologous <em>hPOT1 L259S</em> mutation. We found that the homozygous <em>Pot1a</em><sup><em>L261S</em></sup> mice show shorter telomeres and degenerative pathologies in the intestine, testes, and lungs at old ages, a phenotype that is aggravated with increasing mouse generations, in striking analogy to the telomerase-deficient mouse models. Furthermore, we found that the POT1a-L261S mutant protein binds more strongly to TPP1 and to telomerase and impedes telomerase-dependent telomere lengthening in vivo. We show that telomerase activity at telomeres is reduced in the presence of POT1a-L261S, which behaves as a dominant negative mutant, thus providing a potential mechanism by which <em>Pot1a</em><sup><em>L261S</em></sup> knock-in mice phenocopy the short telomere phenotype of the telomerase knockout model.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"67 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Igf2 regulates early postnatal DPP4+ preadipocyte pool expansion","authors":"Irem Altun, Khanh Ho Diep Vo, Safal Walia, Xiaocheng Yan, Inderjeet Singh, Ruth Karlina, Viktorian Miok, Lingru Kang, Valentin Kenneth Reichenbach, Andreas Israel, Dominik Lutter, Fabiana Perrochi, Siegfried Ussar","doi":"10.1101/gad.352710.125","DOIUrl":"https://doi.org/10.1101/gad.352710.125","url":null,"abstract":"Adipose tissue is rapidly expanding early in life. Elucidating the queues facilitating this process will advance our understanding of metabolically healthy obesity. Using single-cell RNA sequencing, we identified compositional differences of prewean and adult murine subcutaneous adipose tissue. We identified a dipeptidyl peptidase-4 (<em>Dpp4</em>)-positive precursor population residing in the reticular interstitium of subcutaneous adipose expressing insulin growth factor 2 (<em>Igf2</em>) in prewean mice. We show that IGF2 drives proliferation rather than differentiation in these cells. Moreover, loss of <em>Igf2</em> in <em>Dpp4</em><sup>+</sup> progenitor cells promotes adipogenesis. Our findings unravel the temporally restricted expression of <em>Igf2</em> to promote preadipocyte expansion.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"308 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Davys H. Lopez, Kevin D. Rostam, Sumaira Zamurrad, Shuwa Xu, Richard S. Mann
{"title":"A critical affinity window for IgSF proteins DIP-α and Dpr10 is required for proper motor neuron arborization","authors":"Davys H. Lopez, Kevin D. Rostam, Sumaira Zamurrad, Shuwa Xu, Richard S. Mann","doi":"10.1101/gad.352936.125","DOIUrl":"https://doi.org/10.1101/gad.352936.125","url":null,"abstract":"For neurons to establish the correct connections in animal nervous systems, interactions between cell adhesion molecules (CAMs), expressed presynaptically and postsynaptically, are thought to guide neurons to their targets. Here, we assess the role that affinity between two cognate CAMs—DIP-α and Dpr10—plays in establishing the leg neuromuscular system in <em>Drosophila</em>. If affinity decreases or, surprisingly, increases past certain thresholds, motor neuron (MN) terminal branches fail to be maintained. Live imaging during development shows that when affinities are aberrant, MN filopodia are unable to productively engage their muscle targets. Thus, CAM affinities are tuned to achieve proper neuronal morphology.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"25 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavel A. Vlasov, Koichi Ogami, Elizabeth Valenzuela, Risa Karakida Kawaguchi, Marko Jovanovic, James L. Manley
{"title":"Multiple human enhancer RNAs contain long translated open reading frames","authors":"Pavel A. Vlasov, Koichi Ogami, Elizabeth Valenzuela, Risa Karakida Kawaguchi, Marko Jovanovic, James L. Manley","doi":"10.1101/gad.352944.125","DOIUrl":"https://doi.org/10.1101/gad.352944.125","url":null,"abstract":"Enhancer RNAs (eRNAs) are transcribed by <em>RNA polymerase II</em>during enhancer activation but are typically rapidly degraded in the nucleus. During states of reduced RNA surveillance, however, eRNAs and other similar “noncoding” RNAs (including, e.g., upstream antisense RNAs) are stabilized, and some are exported to the cytoplasm and can even be found on polysomes. Here, we report unexpectedly that ∼12% of human intergenic eRNAs contain long open reading frames (>300 nt), many of which can be actively translated, as determined by ribosome profiling, and produce proteins that accumulate in cells, as shown by mass spectrometry (MS) data. Focusing on the largest of the encoded proteins, which we designated as eORFs, which can be up to ∼45 kDa, we found, remarkably, that most are highly basic, with pIs >11.5. This unusual chemistry reflects a striking overabundance of arginine residues and occurs despite a relative paucity of lysines. Exogenous expression of the 10 largest eORFs revealed that they accumulate stably in cells as full-length proteins, and most localize to the nucleus and associate with chromatin. Identification of interacting proteins by MS suggested possible roles for these proteins in several nuclear processes. The eORFs studied are well conserved among primates, though they are largely absent from other mammals. Notably, several contain human-specific C-terminal extensions and display properties suggestive of de novo gene birth. In summary, we have discovered that a fraction of human eRNAs can function as mRNAs, revealing a new and unexpected role for these transcripts.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"31 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariano F. Zacarías-Fluck, Daniel Massó-Vallés, Fabio Giuntini, Íñigo González-Larreategui, Jastrinjan Kaur, Sílvia Casacuberta-Serra, Toni Jauset, Sandra Martínez-Martín, Génesis Martín-Fernández, Erika Serrano del Pozo, Laia Foradada, Judit Grueso, Lara Nonell, Marie-Eve Beaulieu, Jonathan R. Whitfield, Laura Soucek
{"title":"Corrigendum: Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma","authors":"Mariano F. Zacarías-Fluck, Daniel Massó-Vallés, Fabio Giuntini, Íñigo González-Larreategui, Jastrinjan Kaur, Sílvia Casacuberta-Serra, Toni Jauset, Sandra Martínez-Martín, Génesis Martín-Fernández, Erika Serrano del Pozo, Laia Foradada, Judit Grueso, Lara Nonell, Marie-Eve Beaulieu, Jonathan R. Whitfield, Laura Soucek","doi":"10.1101/gad.352999.125","DOIUrl":"https://doi.org/10.1101/gad.352999.125","url":null,"abstract":"<strong>Genes & Development 37:</strong> 303–320 (2023)","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"29 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}