Volume 21 Issue 5, May 2019

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.

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.

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.

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.

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

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.

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.

Chu et al. identify the lipoxygenase ALOX12 as essential for p53-dependent ferroptosis in a pathway independent of GPX4. Monoallelic deletion of Alox12 abrogates p53-mediated suppression in a model of Eµ-Myc-driven lymphoma.

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.

Using platinum replica electron microscopy, Yang and Svitkina find how myosin II enhances actin-mediated mitochondrial constriction and fission.

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.

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.

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.

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