Nature Structural & Molecular Biology最新文献

Putting together pieces of the LIN28A pathway puzzle 拼凑 LIN28A 通路拼图

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-08-21 DOI: 10.1038/s41594-024-01380-w

Alperen Yilmaz, Gulben Gurhan, Jacob H. Hanna

引用次数: 0

Sex chromosome-encoded protein homologs: current progress and open questions 性染色体编码蛋白同源物：当前进展与未决问题

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-08-09 DOI: 10.1038/s41594-024-01362-y

Michael C. Owens, Amber Yanas, Kathy Fange Liu

{"title":"Sex chromosome-encoded protein homologs: current progress and open questions","authors":"Michael C. Owens, Amber Yanas, Kathy Fange Liu","doi":"10.1038/s41594-024-01362-y","DOIUrl":"10.1038/s41594-024-01362-y","url":null,"abstract":"The complexity of biological sex differences is markedly evident in human physiology and pathology. Although many of these differences can be ascribed to the expression of sex hormones, another contributor to sex differences lies in the sex chromosomes beyond their role in sex determination. Although largely nonhomologous, the human sex chromosomes express seventeen pairs of homologous genes, referred to as the ‘X–Y pairs.’ The X chromosome-encoded homologs of these Y-encoded proteins are crucial players in several cellular processes, and their dysregulation frequently results in disease development. Many diseases related to these X-encoded homologs present with sex-biased incidence or severity. By contrast, comparatively little is known about the differential functions of the Y-linked homologs. Here, we summarize and discuss the current understanding of five of these X–Y paired proteins, with recent evidence of differential functions and of having a potential link to sex biases in disease, highlighting how amino acid-level sequence differences may differentiate their functions and contribute to sex biases in human disease. Here, the authors examine and discuss the functional complexity and cellular implications of X–Y pairs, homologous genes expressed in the human sex chromosomes.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908894","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}

引用次数: 0

Identifying nature’s smallest fractals 识别自然界最小的分形

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-30 DOI: 10.1038/s41594-024-01368-6

Kelli L. Hvorecny

引用次数: 0

Poised PABP–RNA hubs implement signal-dependent mRNA decay in development 定位的 PABP-RNA 中枢在发育过程中实现了信号依赖性 mRNA 衰减。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-25 DOI: 10.1038/s41594-024-01363-x

Miha Modic, Klara Kuret, Sebastian Steinhauser, Rupert Faraway, Emiel van Genderen, Igor Ruiz de Los Mozos, Jona Novljan, Žiga Vičič, Flora C. Y. Lee, Derk ten Berge, Nicholas M. Luscombe, Jernej Ule

{"title":"Poised PABP–RNA hubs implement signal-dependent mRNA decay in development","authors":"Miha Modic, Klara Kuret, Sebastian Steinhauser, Rupert Faraway, Emiel van Genderen, Igor Ruiz de Los Mozos, Jona Novljan, Žiga Vičič, Flora C. Y. Lee, Derk ten Berge, Nicholas M. Luscombe, Jernej Ule","doi":"10.1038/s41594-024-01363-x","DOIUrl":"10.1038/s41594-024-01363-x","url":null,"abstract":"Signaling pathways drive cell fate transitions largely by changing gene expression. However, the mechanisms for rapid and selective transcriptome rewiring in response to signaling cues remain elusive. Here we use deep learning to deconvolve both the sequence determinants and the trans-acting regulators that trigger extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase kinase (MEK)-induced decay of the naive pluripotency mRNAs. Timing of decay is coupled to embryo implantation through ERK–MEK phosphorylation of LIN28A, which repositions pLIN28A to the highly A+U-rich 3′ untranslated region (3′UTR) termini of naive pluripotency mRNAs. Interestingly, these A+U-rich 3′UTR termini serve as poly(A)-binding protein (PABP)-binding hubs, poised for signal-induced convergence with LIN28A. The multivalency of AUU motifs determines the efficacy of pLIN28A–PABP convergence, which enhances PABP 3′UTR binding, decreases the protection of poly(A) tails and activates mRNA decay to enable progression toward primed pluripotency. Thus, the signal-induced convergence of LIN28A with PABP–RNA hubs drives the rapid selection of naive mRNAs for decay, enabling the transcriptome remodeling that ensures swift developmental progression. Here the authors show that, upon embryo implantation, signaling triggers a large-scale rearrangement of protein–RNA interactions. Phosphorylated LIN28A reassembles onto the 3′ untranslated region termini of pluripotency-associated mRNAs, where it converges with the binding of poly(A)-binding protein and drives selective mRNA decay.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01363-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs 决定 let-7 pre-miRNA 命运的聚合酶活性转换的结构基础。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-25 DOI: 10.1038/s41594-024-01357-9

Gangshun Yi, Mingda Ye, Loic Carrique, Afaf El-Sagheer, Tom Brown, Chris J. Norbury, Peijun Zhang, Robert J. C. Gilbert

{"title":"Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs","authors":"Gangshun Yi, Mingda Ye, Loic Carrique, Afaf El-Sagheer, Tom Brown, Chris J. Norbury, Peijun Zhang, Robert J. C. Gilbert","doi":"10.1038/s41594-024-01357-9","DOIUrl":"10.1038/s41594-024-01357-9","url":null,"abstract":"Tumor-suppressor let-7 pre-microRNAs (miRNAs) are regulated by terminal uridylyltransferases TUT7 and TUT4 that either promote let-7 maturation by adding a single uridine nucleotide to the pre-miRNA 3′ end or mark them for degradation by the addition of multiple uridines. Oligo-uridylation is increased in cells by enhanced TUT7/4 expression and especially by the RNA-binding pluripotency factor LIN28A. Using cryogenic electron microscopy, we captured high-resolution structures of active forms of TUT7 alone, of TUT7 plus pre-miRNA and of both TUT7 and TUT4 bound with pre-miRNA and LIN28A. Our structures reveal that pre-miRNAs engage the enzymes in fundamentally different ways depending on the presence of LIN28A, which clamps them onto the TUTs to enable processive 3′ oligo-uridylation. This study reveals the molecular basis for mono- versus oligo-uridylation by TUT7/4, as determined by the presence of LIN28A, and thus their mechanism of action in the regulation of cell fate and in cancer. Here, the authors show that cytoplasmic uridylyltransferases TUT7 and TUT4 bind let-7 pre-miRNA by alternative means in the absence and presence of Lin28A, which directly interacts with both RNA and enzyme to convert from a distributive to a processive mode of action.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01357-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The power of scientific collaborations and the future of structural biology 科学合作的力量与结构生物学的未来

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-15 DOI: 10.1038/s41594-024-01358-8

Pedro Beltrao

引用次数: 0

AlphaFold3 takes a step toward decoding molecular behavior and biological computation AlphaFold3 向解码分子行为和生物计算迈出了一步

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-08 DOI: 10.1038/s41594-024-01350-2

Rohit Roy, Hashim M. Al-Hashimi

引用次数: 0

Obscure DNA sequences unveil a new cancer target 晦涩难懂的 DNA 序列揭示了新的癌症靶点

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-08 DOI: 10.1038/s41594-024-01347-x

Agnel Sfeir

引用次数: 0

Cryo-EM structures of γ-TuRC reveal molecular insights into microtubule nucleation γ-TuRC的低温电子显微镜结构揭示了微管成核的分子奥秘

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-02 DOI: 10.1038/s41594-024-01345-z

Léa Mammri, Paul T. Conduit

引用次数: 0

Structure of the poxvirus core 痘病毒核心的结构

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-18 DOI: 10.1038/s41594-024-01331-5

Fasséli Coulibaly

引用次数: 0