Todd Locklear (editorhelmet5)

Aging is an inevitable process that involves profound physiological changes. Long non-coding RNAs (lncRNAs) are emerging as important regulators in various biological processes but are not systemically studied in aging. To provide an organism-wide lncRNA landscape during aging, we conduct comprehensive RNA sequencing (RNA-seq) analyses across the mouse lifespan. Of the 1,675 aging-regulated lncRNAs (AR-lncRNAs) identified, the majority are connected to inflammation-related biological pathways. AR-lncRNAs exhibit high tissue specificity; conversely, those with higher tissue specificity are preferentially regulated during aging. White adipose tissue (WAT) displays the highest number of AR-lncRNAs and develops the most dynamic crosstalk between AR-lncRNA and AR-mRNA during aging. An adipose-enriched AR-lncRNA, lnc-adipoAR1, is negatively correlated with aging, and knocking it down inhibits adipogenesis, phenocopying the compromised adipogenic capacity of aged fat. Our works together reveal AR-lncRNAs as essential components in aging and suggest that although each tissue ages in a distinct manner, WAT is a leading contributor to aging-related health decline.Genome stability requires coordination of DNA replication origin activation and replication fork progression. RTEL1 is a regulator of homologous recombination (HR) implicated in meiotic cross-over control and DNA repair in C. elegans. Through a genome-wide synthetic lethal screen, we uncovered an essential genetic interaction between RTEL1 and DNA polymerase (Pol) epsilon. Loss of POLE4, an accessory subunit of Pol epsilon, has no overt phenotype in worms. In contrast, the combined loss of POLE-4 and RTEL-1 results in embryonic lethality, accumulation of HR intermediates, genome instability, and cessation of DNA replication. Similarly, loss of Rtel1 in Pole4-/- mouse cells inhibits cellular proliferation, which is associated with persistent HR intermediates and incomplete DNA replication. We propose that RTEL1 facilitates genome-wide fork progression through its ability to metabolize DNA secondary structures that form during DNA replication. Loss of this function becomes incompatible with cell survival under conditions of reduced origin activation, such as Pol epsilon hypomorphy.Balanced stem cell self-renewal and differentiation is essential for maintaining tissue homeostasis, but the underlying mechanisms are poorly understood. Here, we identified the transcription factor SRY-related HMG-box (Sox) 100B, which is orthologous to mammalian Sox8/9/10, as a common target and central mediator of the EGFR/Ras and JAK/STAT signaling pathways that coordinates intestinal stem cell (ISC) proliferation and differentiation during both normal epithelial homeostasis and stress-induced intestinal repair in Drosophila. The two stress-responsive pathways directly regulate Sox100B transcription via two separate enhancers. Interestingly, an appropriate level of Sox100B is critical for its function, as its depletion inhibits ISC proliferation via cell cycle arrest, while its overexpression also inhibits ISC proliferation by directly suppressing EGFR expression and additionally promotes ISC differentiation by activating a differentiation-promoting regulatory circuitry composed of Sox100B, Sox21a, and Pdm1. Selleck Rapamycin Thus, our study reveals a Sox family transcription factor that functions as a stress-responsive signaling nexus that ultimately controls tissue homeostasis and regeneration.Centrosome separation in late G2/ early prophase requires precise spatial coordination that is determined by a balance of forces promoting and antagonizing separation. The major effector of centrosome separation is the kinesin Eg5. However, the identity and regulation of Eg5-antagonizing forces is less well characterized. By manipulating candidate components, we find that centrosome separation is reversible and that separated centrosomes congress toward a central position underneath the flat nucleus. Thi