Trends in Cell Biology最新文献

Ferroptosis is programmed cell death induced by iron-driven lipid peroxidation. Numerous studies have shown that ferroptosis is implicated in the progression of colorectal cancer (CRC) and has emerged as a promising strategy to combat therapy-resistant CRC. While the intrinsic antiferroptotic and proferroptotic pathways in CRC cells have been well characterized, extrinsic metabolism pathways regulating ferroptosis in CRC pathogenesis remain less understood. Emerging evidence shows that gut microbial metabolism is tightly correlated with the progression of CRC. This review provides an overview of gut microbial metabolism and discusses how these metabolites derived from intestinal microflora contribute to cancer plasticity through ferroptosis. Targeting gut microbe-mediated ferroptosis is a potential approach for CRC treatment.

The highly proliferative gut tissue exhibits rapid telomere shortening with systemic effects on the host organism. Recent studies have demonstrated a bidirectionality in interactions between intestinal telomere length dynamics and the composition and activity of the gut microbiome thus linking processes of inflammation, dysbiosis and aging across different vertebrate species.

The ability of a cell to properly express its genes depends on optimal transcription and splicing. RNA polymerase II (RNAPII) transcribes protein-coding genes and produces pre-mRNAs, which undergo, largely co-transcriptionally, intron excision by the spliceosome complex. Spliceosome activation is a major control step, leading to a catalytically active complex. Recent work has showed that cyclin-dependent kinase (CDK)11 regulates spliceosome activation via the phosphorylation of SF3B1, a core spliceosome component. Thus, CDK11 arises as a major coordinator of gene expression in metazoans due to its role in the rate-limiting step of pre-mRNA splicing. This review outlines the evolution of CDK11 and SF3B1 and their emerging roles in splicing regulation. It also discusses how CDK11 and its inhibition affect transcription and cell cycle progression.

The spatial segregation of the genome into compartments is a major feature of 3D genome organization. New data on mammalian chromosome organization across different conditions reveal important information about how and why these compartments form and change. A combination of epigenetic state, nuclear body tethering, physical forces, gene expression, and replication timing (RT) can all influence the establishment and alteration of chromosome compartments. We review the causes and implications of genomic regions undergoing a 'compartment switch' that changes their physical associations and spatial location in the nucleus. About 20-30% of genomic regions change compartment during cell differentiation or cancer progression, whereas alterations in response to a stimulus within a cell type are usually much more limited. However, even a change in 1-2% of genomic bins may have biologically relevant implications. Finally, we review the effects of compartment changes on gene regulation, DNA damage repair, replication, and the physical state of the cell.

Embryonic and adult stem cells enable development and regeneration. Embryonic cells, like adult stem cells, can enter dormancy as part of their lifecycle. Recent evidence suggests that this cellular transition to dormancy requires active rewiring of metabolism. The dormancy-induced metabolic switches in embryonic and adult stem cells are explored here.

In neurodegeneration, neurons release lipids that accumulate in glial lipid droplets (LDs). But what controls lipid transport and how does this affect glia? A recent study by Li et al. discovered that the loss of neuronal AMP-activated protein kinase (AMPK) activity promotes lipid efflux, which drives a proinflammatory state in microglia.

RNA G-quadruplexes (rG4s) are noncanonical secondary structures formed by guanine-rich sequences that are found in different regions of RNA molecules. These structures have been implicated in diverse biological processes, including translation, splicing, and RNA stability. Recent studies have suggested that rG4s play a role in the cellular response to stress. This review summarizes the current knowledge on rG4s under stress, focusing on their formation, regulation, and potential functions in stress response pathways. We discuss the molecular mechanisms that regulate the formation of rG4 under different stress conditions and the impact of these structures on RNA metabolism, gene expression, and cell survival. Finally, we highlight the potential therapeutic implications of targeting rG4s for the treatment of stress-related diseases through modulating cell survival.

The importance of post-translational modifications (PTMs), particularly O-GlcNAcylation, of cytoplasmic proteins in apoptosis has been neglected for quite a while. Modification of cytoplasmic proteins by a single N-acetylglucosamine sugar is a dynamic and reversible PTM exhibiting properties more like phosphorylation than classical O- and N-linked glycosylation. Due to the sparse information existing, we have only limited understanding of how GlcNAcylation affects cell death. Deciphering the role of GlcNAcylation in cell fate may provide further understanding of cell fate decisions. This review focus on the modulation of extrinsic apoptotic pathway via GlcNAcylation carried out by O-GlcNAc transferase (OGT) or by other bacterial effector proteins.