Volume 28 Issue 6, June 2021

The RNA methyltransferase METTL3 catalyzes N⁶-methyladenosine (m⁶A) modification of messenger RNAs (mRNAs). It is overexpressed in many types of cancer, including acute myelogenous leukemia (AML), and promotes cancer cell growth and tumorigenicity. Now, a selective small molecule inhibitor of METTL3 shows significant antileukemic effects in preclinical AML models, highlighting the promise of pharmacological METTL3 inhibition as a new cancer therapy.

The first crystal structure of a membrane-bound fatty acid elongase condensing enzyme, human ELOVL7, reveals a new reaction mechanism.

The organization of multiple steps of the RNA life cycle in phase-separated condensates presents a framework for understanding how sequestration of RNA-binding proteins and RNAs modulates gene expression.

Structural characterization of B6, a monoclonal antibody that cross-reacts with eight β-coronavirus spike proteins from three viral lineages, reveals a conserved cryptic epitope that could serve as a target for structure-guided design of a pan-β-coronavirus vaccine.

Cell-based, in vitro and in vivo assays reveal that Fanconi anemia factors function in a BRCA1-dependent BIR-like pathway to restart stalled replication forks and that persistent replication stress contributes to FA pathogenesis.

Chemical genetic dissection of the SWI/SNF–Polycomb axis in mouse stem cells identifies an unexpected role for mSWI/SNF in repression, providing mechanistic insight into the dynamic ‘tug of war’ between transcriptional activation and repression.

ELOVLs are membrane-embedded enzymes that elongate very long chain fatty acids, precursors of sphingolipids and ceramides. The first crystal structure of a human ELOVL reveals an unexpected reaction mechanism, suggesting potential approaches for inhibition in disease.

High-throughput chemical screening identifies retinoic acid signaling as a regulatory pathway of 2-cell-like cell reprogramming and early mouse development.