Browse Articles

  • Article |

    Grainger et al. demonstrate that, in zebrafish and human cells, EGFR-mediated phosphorylation of Fzd9b promotes internalization of the Wnt9a–Fzd9b–LRP signalosome and subsequent signal transduction.

    • Stephanie Grainger
    • , Nicole Nguyen
    • , Jenna Richter
    • , Jordan Setayesh
    • , Brianna Lonquich
    • , Chet Huan Oon
    • , Jacob M. Wozniak
    • , Rocio Barahona
    • , Caramai N. Kamei
    • , Jack Houston
    • , Marvic Carrillo-Terrazas
    • , Iain A. Drummond
    • , David Gonzalez
    • , Karl Willert
    •  & David Traver
  • News & Views |

    IRE1α is an endoplasmic reticulum (ER) transmembrane protein known for a crucial role in regulating the unfolding protein response. A study now shows that IRE1α interacts with the main ER Ca2+ channel InsP3Rs and facilitates the transfer of Ca2+ from the ER into mitochondria, thus driving cellular metabolism.

    • Roland Malli
    •  & Wolfgang F. Graier
  • Article |

    Carreras-Sureda et al. uncover a non-canonical role for IRE1α as a scaffold that stabilizes InsP3Rs at MAMs to control calcium uptake, fine-tunes ER–mitochondrial communication and regulates energy metabolism via AMPK.

    • Amado Carreras-Sureda
    • , Fabián Jaña
    • , Hery Urra
    • , Sylvere Durand
    • , David E. Mortenson
    • , Alfredo Sagredo
    • , Galdo Bustos
    • , Younis Hazari
    • , Eva Ramos-Fernández
    • , Maria L. Sassano
    • , Philippe Pihán
    • , Alexander R. van Vliet
    • , Matías González-Quiroz
    • , Angie K. Torres
    • , Cheril Tapia-Rojas
    • , Martijn Kerkhofs
    • , Rubén Vicente
    • , Randal J. Kaufman
    • , Nibaldo C. Inestrosa
    • , Christian Gonzalez-Billault
    • , R. Luke Wiseman
    • , Patrizia Agostinis
    • , Geert Bultynck
    • , Felipe A. Court
    • , Guido Kroemer
    • , J. César Cárdenas
    •  & Claudio Hetz
  • Article |

    Necroptosis drives arthritis. Polykratis et al. show that the deubiquitinating enzyme A20 inhibits inflammasome-dependent arthritis development by regulating macrophage necroptosis and this function depends on its ZnF7 ubiquitin binding domain.

    • Apostolos Polykratis
    • , Arne Martens
    • , Remzi Onur Eren
    • , Yoshitaka Shirasaki
    • , Mai Yamagishi
    • , Yoshifumi Yamaguchi
    • , Sotaro Uemura
    • , Masayuki Miura
    • , Bernhard Holzmann
    • , George Kollias
    • , Marietta Armaka
    • , Geert van Loo
    •  & Manolis Pasparakis
  • News & Views |

    Yap signalling is crucial for intestinal regeneration, but its role is largely dispensable in homeostasis. Two studies now reveal Yap-dependent mechanisms of intestinal regeneration and tissue organization: transient expansion of a rare cell type after damage in vivo and Notch–Dll activation for symmetry breaking in organoid development.

    • Vivian S. W. Li
  • Editorial |

    RNA molecules are more than messengers between DNA and protein and exhibit rich regulatory functions in development and disease. In this issue, we present a Focus on regulatory RNAs with specially commissioned Review articles that discuss recent advances in this fast-growing area.

  • News & Views |

    Rag GTPases play a crucial role in mTORC1 activation by promoting its recruitment to the lysosomal surface in a nutrient-dependent manner. A study now identifies a family of lysosomal G-protein-coupled receptors as modulators of Rag GTPases localization and activation, adding one more component to the fast-growing mTOR regulatory network.

    • Rosa Puertollano
  • Review Article |

    Yao et al. review functions of lncRNAs in controlling chromatin architecture, transcription and nuclear bodies in the nucleus and in modulating mRNA stability, translation and protein modifications in the cytoplasm.

    • Run-Wen Yao
    • , Yang Wang
    •  & Ling-Ling Chen
  • Review Article |

    Sylvain et al. review cellular functions of various RNA modifications and their roles in regulating cell fate in normal and cancer tissues.

    • Sylvain Delaunay
    •  & Michaela Frye
  • News & Views |

    Haematopoietic stem cells (HSCs) are maintained in vivo by intrinsic programs and extrinsic niche signals. Ex vivo expansion of HSCs is limited, owing to reduced stem cell maintenance factors. A study now shows that rejuvenated niche cells can be obtained by transcriptional rewiring of specific genes that maintain and expand HSCs ex vivo.

    • Aparna Venkatraman
    •  & Linheng Li
  • Article |

    Gan et al. identify the GPCR-like protein GPR137B that interacts with Rag GTPases to recruit mTORC1 to lysosomes. They show that GPR137B controls dynamic Rag and mTORC1 activity as well as lysosome morphology.

    • Lin Gan
    • , Akiko Seki
    • , Kimberle Shen
    • , Harini Iyer
    • , Kyuho Han
    • , Arnold Hayer
    • , Roy Wollman
    • , Xuecai Ge
    • , Jerry R. Lin
    • , Gautam Dey
    • , William S. Talbot
    •  & Tobias Meyer
  • Resource |

    Xia and colleagues provided a map for transcriptome-wide distribution of m6A RNA methylation in eight human fetal tissue types.

    • Shan Xiao
    • , Shuo Cao
    • , Qitao Huang
    • , Linjian Xia
    • , Mingqiang Deng
    • , Mengtian Yang
    • , Guiru Jia
    • , Xiaona Liu
    • , Junfang Shi
    • , Weishi Wang
    • , Yuan Li
    • , Sun Liu
    • , Haoran Zhu
    • , Kaifen Tan
    • , Qizhi Luo
    • , Mei Zhong
    • , Chunjiang He
    •  & Laixin Xia
  • Article |

    Atlasi et al. demonstrate that transcriptome and epigenome resetting during serum-to-2i pluripotency conversion involves minimal enhancer–promoter rewiring and is instead linked to 2i-enhancer activation via Esrrb-mediated H3K27 acetylation.

    • Yaser Atlasi
    • , Wout Megchelenbrink
    • , Tianran Peng
    • , Ehsan Habibi
    • , Onkar Joshi
    • , Shuang-Yin Wang
    • , Cheng Wang
    • , Colin Logie
    • , Ina Poser
    • , Hendrik Marks
    •  & Hendrik G. Stunnenberg
  • News & Views |

    Components of the spliceosome are frequently mutated in haematopoietic malignancies. Identification of mis-spliced genes promoting transformation will uncover novel targeted therapies. Now, a long isoform of IRAK4 is shown to be upregulated in a subset of acute myeloid leukaemia patients, conferring susceptibility for IRAK4 inhibition therapy.

    • Maria Guillamot
    •  & Iannis Aifantis
  • Article |

    Smith et al demonstrate that mutated splicing factor U2AF1 promotes expression of a longer isoform of IRAK4, leading to enhanced NF-kB activation and leukaemic growth in acute myeloid leukaemia.

    • Molly A. Smith
    • , Gaurav S. Choudhary
    • , Andrea Pellagatti
    • , Kwangmin Choi
    • , Lyndsey C. Bolanos
    • , Tushar D. Bhagat
    • , Shanisha Gordon-Mitchell
    • , Dagny Von Ahrens
    • , Kith Pradhan
    • , Violetta Steeples
    • , Sanghyun Kim
    • , Ulrich Steidl
    • , Matthew Walter
    • , Iain D. C. Fraser
    • , Aishwarya Kulkarni
    • , Nathan Salomonis
    • , Kakajan Komurov
    • , Jacqueline Boultwood
    • , Amit Verma
    •  & Daniel T. Starczynowski
  • Article |

    Esposito et al. report a role for bone vascular niche E-selectin in promoting mesenchymal–epithelial transition and Wnt signalling in breast cancer cells, thereby enhancing bone metastasis.

    • Mark Esposito
    • , Nandini Mondal
    • , Todd M. Greco
    • , Yong Wei
    • , Chiara Spadazzi
    • , Song-Chang Lin
    • , Hanqiu Zheng
    • , Corey Cheung
    • , John L. Magnani
    • , Sue-Hwa Lin
    • , Ileana M. Cristea
    • , Robert Sackstein
    •  & Yibin Kang
  • Letter |

    Nakahara et al. identify five transcriptional regulators that can revitalize Nestin-expressing mesenchymal stromal cells to enhance the synthesis of haematopoietic stem cell niche factors, improve haematopoietic stem cell expansion and protect them against DNA damage.

    • Fumio Nakahara
    • , Daniel K. Borger
    • , Qiaozhi Wei
    • , Sandra Pinho
    • , Maria Maryanovich
    • , Ali H. Zahalka
    • , Masako Suzuki
    • , Cristian D. Cruz
    • , Zichen Wang
    • , Chunliang Xu
    • , Philip E. Boulais
    • , Avi Ma’ayan
    • , John M. Greally
    •  & Paul S. Frenette
  • Article |

    Unlike many other formin actin assembly factors, INF2 is not autoinhibited. Higgs and colleagues find that INF2 is inhibited by cyclase-associated protein and acetylated actin through a mechanism they name facilitated autoinhibition.

    • Mu A
    • , Tak Shun Fung
    • , Arminja N. Kettenbach
    • , Rajarshi Chakrabarti
    •  & Henry N. Higgs
  • News & Views |

    Osteoclasts are known for their role in bone resorption. A study now shows that a vascular–associated osteoclast subtype at the growth plate also regulates blood vessel growth in bone and is supported by type H endothelial cells. These type H capillaries, in turn, release proteinases that promote cartilage degradation.

    • Jameel Iqbal
    •  & Mone Zaidi
  • Article |

    Chen et al. show that tumour-associated macrophages transmit HIF-1α-stabilizing long noncoding RNA through extracellular vesicles to breast cancer cells, thereby enhancing tumour glycolysis and chemoresistance.

    • Fei Chen
    • , Jianing Chen
    • , Linbin Yang
    • , Jiang Liu
    • , Xiaoqian Zhang
    • , Yin Zhang
    • , Qingqiang Tu
    • , Dong Yin
    • , Dechen Lin
    • , Ping-Pui Wong
    • , Di Huang
    • , Yue Xing
    • , Jinghua Zhao
    • , Mengfeng Li
    • , Qiang Liu
    • , Fengxi Su
    • , Shicheng Su
    •  & Erwei Song
  • News & Views |

    MicroRNAs (miRNAs) repress target mRNAs, often with exquisite tissue specificity. Wang et al. exploit the specific expression of miRNAs to regulate guide production for Cas9. Their method enables novel strategies to simultaneously measure the activity of multiple miRNAs and restrict Cas9 binding or genome editing to precisely defined cell types.

    • Karina Jouravleva
    •  & Phillip D. Zamore
  • Article |

    Nguyen et al. show that neuropsin (OPN5) suppresses hyaloid vessel regression in the developing mouse retina in response to light, by regulation of the dopamine reuptake transporter and DRD2-dependent suppression of VEGFR2 activity.

    • Minh-Thanh T. Nguyen
    • , Shruti Vemaraju
    • , Gowri Nayak
    • , Yoshinobu Odaka
    • , Ethan D. Buhr
    • , Nuria Alonzo
    • , Uyen Tran
    • , Matthew Batie
    • , Brian A. Upton
    • , Martin Darvas
    • , Zbynek Kozmik
    • , Sujata Rao
    • , Rashmi S. Hegde
    • , P. Michael Iuvone
    • , Russell N. Van Gelder
    •  & Richard A. Lang
  • News & Views |

    HIV particles incorporate host membrane proteins into their envelope to evade the immune system and infect other cells. A study now shows that Gag assembly on the host cell membrane produces a raft-like nanodomain favourable for protein partitioning due to a transbilayer coupling mechanism assisted by long saturated chain lipids and cholesterol.

    • Joanna Podkalicka
    •  & Patricia Bassereau
  • Article |

    Boos et al. show that impairing mitochondrial protein import induces a global transcriptional response to activate the ubiquitin–proteasome system and heat stress response and repress oxidative phosphorylation genes.​

    • Felix Boos
    • , Lena Krämer
    • , Carina Groh
    • , Ferris Jung
    • , Per Haberkant
    • , Frank Stein
    • , Florian Wollweber
    • , Adrian Gackstatter
    • , Eva Zöller
    • , Martin van der Laan
    • , Mikhail M. Savitski
    • , Vladimir Benes
    •  & Johannes M. Herrmann
  • Article |

    Choi et al. show that the stability of nuclear stress-activated wild-type and mutant p53 is regulated by the type I phosphatidylinositol phosphate kinase PIPK1-α and the lipid messenger PtdIns(4,5)P2.

    • Suyong Choi
    • , Mo Chen
    • , Vincent L. Cryns
    •  & Richard A. Anderson
  • News & Views |

    Macrophages modulate mammary tumour response to chemotherapy. A new study shows that targeted elimination of macrophages elicits a type I interferon response in the tumour microenvironment that enhances the efficacy of platinum- but not taxane-based chemotherapy, underscoring complex regulatory roles for macrophages in chemotherapy-treated tumours.

    • Michele De Palma
    • , Sina Nassiri
    •  & Chiara Cianciaruso
  • Article |

    Salvagno et al. demonstrated that blocking tumour-associated macrophages in breast cancer enhances the efficacy of chemotherapeutics by promoting intratumoural type I interferon responses.

    • Camilla Salvagno
    • , Metamia Ciampricotti
    • , Sander Tuit
    • , Cheei-Sing Hau
    • , Antoinette van Weverwijk
    • , Seth B. Coffelt
    • , Kelly Kersten
    • , Kim Vrijland
    • , Kevin Kos
    • , Thomas Ulas
    • , Ji-Ying Song
    • , Chia-Huey Ooi
    • , Dominik Rüttinger
    • , Philippe A. Cassier
    • , Jos Jonkers
    • , Joachim L. Schultze
    • , Carola H. Ries
    •  & Karin E. de Visser
  • Article |

    Zhao et al. find that AMPK phosphorylates and activates the mitochondrial Ca2+ uniporter in response to low energy status in mitosis, allowing Ca2+ entry into mitochondria to boost mitochondrial respiration.

    • Haixin Zhao
    • , Teng Li
    • , Kai Wang
    • , Fei Zhao
    • , Jiayi Chen
    • , Guang Xu
    • , Jie Zhao
    • , Ting Li
    • , Liang Chen
    • , Lin Li
    • , Qing Xia
    • , Tao Zhou
    • , Hui-Yan Li
    • , Ai-Ling Li
    • , Toren Finkel
    • , Xue-Min Zhang
    •  & Xin Pan
  • News & Views |

    Epithelial–mesenchymal transition (EMT) is crucial for development, and for dissemination and invasion of cancer cells. A study now identifies the apical–basolateral polarity status of epithelia as a checkpoint for EMT induction and tumour metastasis through aPKC–Par3-regulated degradation of the EMT transcription factor SNAI1.

    • Oana-Diana Persa
    •  & Carien M. Niessen
  • Letter |

    Nakamura et al. show that DNA repair pathway choice and initiation of homologous recombination is guided by the recruitment of BRCA1 to post-replicative chromatin by BARD1 recognition of histone H4 tails unmethylated on lysine 20.

    • Kyosuke Nakamura
    • , Giulia Saredi
    • , Jordan R. Becker
    • , Benjamin M. Foster
    • , Nhuong V. Nguyen
    • , Tracey E. Beyer
    • , Laura C. Cesa
    • , Peter A. Faull
    • , Saulius Lukauskas
    • , Thomas Frimurer
    • , J. Ross Chapman
    • , Till Bartke
    •  & Anja Groth
  • Article |

    Şentürk et al. show that ubiquilins bind v-ATPase to control lysosome acidity, mTOR signalling and autophagic flux in neurons, and that feeding flies with acidic nanoparticles ameliorates defective autophagy in ubiquilin mutants.

    • Mümine Şentürk
    • , Guang Lin
    • , Zhongyuan Zuo
    • , Dongxue Mao
    • , Emma Watson
    • , Antonios G. Mikos
    •  & Hugo J. Bellen