Many genomic studies have revealed associations between the gut microbiota composition and host metabolism. These observations led to the idea that a causal relationship could exist between the microbiota and metabolic diseases, a concept supported by studies showing compositional changes in the microbial community in metabolic diseases and transmissibility of host phenotype via microbiota transfer

Commensal microbial communities inhabit biological niches in the mammalian host, where they impact the host’s physiology through induction of “colonization resistance” against infections by a multitude of molecular mechanisms. These colonization-regulating activities involve microbe-microbe and microbe-host interactions, which induce, through utilization of complex bacterial networks, competition over

In this issue of Molecular Cell, Gonatopoulos-Pournatzis et al. (2020) report a neuron-specific microexon in eIF4G translation initiation factors that dampens synaptic protein translation. Autism-associated disruption of this exon results in increased protein production, likely through reduced coalescence with cytoplasmic ribonucleoprotein granule components, including FMRP.

In this issue of Molecular Cell, Cossa et al. (2020) uncover the basis for a dependency of tumor cells with deregulated MYC on the kinase NUAK1, which acts through PP1 and PNUTS to ensure that splicing keeps up with MYC-driven transcription.

Distal regulatory elements control gene expression during differentiation. In this issue of Molecular Cell, Barnett et al. (2020) develop a new technology, called ATAC-Me, and discover that removal of DNA methylation is not a pre-requisite for the creation of accessible chromatin at active gene regulatory elements during cellular differentiation.

RNA polymerase II (RNA Pol II) is generally paused at promoter-proximal regions in most metazoans, and based on in vitro studies, this function has been attributed to the negative elongation factor (NELF). Here, we show that upon rapid depletion of NELF, RNA Pol II fails to be released into gene bodies, stopping instead around the +1 nucleosomal dyad-associated region. The transition to the 2nd pause

Okazaki and colleagues report that PD-1 signaling mainly restrains effector function at the early stage of T cell activation. The authors find that cytokine genes require strong antigen stimulation and are more susceptible to PD-1 inhibition.

While gapmers efficiently knock down as well as terminate transcription of nascent lncRNAs and mRNAs, Lee and Mendell (2020) and Lai et al. (2020) also demonstrate that Pol II termination is not observed with gapmers targeting the 3′ terminal portions of the transcript.

Two recent studies have uncovered a novel means by which bacteriophages thwart host immunity. Mendoza et al. (2020) and Malone et al. (2020) demonstrate that a nucleus-like proteinaceous structure shields phage DNA from CRISPR-associated nucleases encompassing Cascade-Cas3, Cas9, and Cas12.

In the current issue of Molecular Cell, Liu et al. (2020) show that the secretion of cancer-linked forms of mutant calreticulin allow cancer cells to escape protective immune responses induced by chemotherapeutic and immunotherapeutic drugs, thereby promoting tumor growth.

To delineate the roles of variant (vPRC1) and canonical (cPRC1) Polycomb repressive complex 1, Blackledge et al. (2020) and Tamburri et al. (2020) elegantly disrupt RING1A/B catalytic activity without affecting stability of either complex and then explore the precise contribution of vPRC1-mediated H2AK119ub1 to Polycomb-mediated gene repression.

A recent paper by Gallagher et al. (2020) demonstrates that c-di-GMP controls spore formation in Streptomyces venezuelae through sequestering the sporulation sigma factor σWhiG and presents the crystal structure of a ternary complex between c-di-GMP, σWhiG, and its anti-sigma factor, RsiG.

Two decades into the twenty-first century, a confluence of breakthrough technologies wielded at the molecular level is presenting biologists with unique opportunities to unravel the complexities of the cellular world. CRISPR/Cas9 allows gene knock-outs, knock-ins, and single-base editing at chromosomal loci. RNA-based tools such as siRNA, antisense oligos, and morpholinos can be used to silence expression