Daria Sobańska

Aging is a progressive weakening of numerous functions of organisms resulting in diminished abilities to safeguard against environmental damage and augment physiological harmony. It is not a disease in itself; however, it is a main cause of debilitating and life‐threatening chronic aging‐related diseases (ARDs). tRNA‐derived fragments (tDRs) are stable forms of tRNAs of 14–35 nt in length that function as regulatory small‐RNA molecules. Here we aimed to perform a systematic review of original articles on the involvement of tDRs in the etiology of ARDs: their identification and characterization. The systematic review was conducted according to the Cochrane Handbook guidelines and the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement. Based on the eligibility criteria defined for the study, 21 original articles were included in this systematic review, covering 11 ARDs. The preferred research method used to study tDRs was high‐throughput sequencing combined with RT‐qPCR, and as a result, a number of tDRs were implicated in ARDs. Importantly, an in‐depth analysis of the articles allowed us to identify several shortcomings: (i) the tDRs nomenclature varies between studies and articles, making it often difficult to precisely identify molecules differentiating in a given disease; (ii) the chosen tDRs have all been studied for a miRNA‐like mechanism of action; however, tDRs also function in RNAi‐independent ways, which need to be studied as well; (iii) to precisely identify tDRs, the sequencing techniques that overcome the issues of modifications harbored by tRNAs must be used.

How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, ranging from emergency medicine to space travel. Studying a hibernation-like response in the free-living nematode Caenorhabditis elegans, we uncovered a regulatory axis that enhances the natural resistance of nematodes to severe cold. This axis involves conserved transcription factors, DAF-16/FoxO and PQM-1, which jointly promote cold survival by upregulating FTN-1, a protein related to mammalian ferritin heavy chain (FTH1). Moreover, we show that inducing expression of FTH1 also promotes cold survival of mammalian neurons, a cell type particularly sensitive to deterioration in hypothermia. Our findings in both animals and cells suggest that FTN-1/FTH1 facilitates cold survival by detoxifying ROS-generating iron species. We finally show that mimicking the effects of FTN-1/FTH1 with drugs protects neurons from cold-induced degeneration, opening a potential avenue to improved treatments of hypothermia.

Regnase-1 is an evolutionarily conserved endoribonuclease. It degrades diverse mRNAs important for many biological processes including immune homeostasis, development and cancer. There are two competing models of Regnase-1-mediated mRNA silencing. One model postulates that Regnase-1 works together with another RNA-binding protein, Roquin-1, which recruits Regnase-1 to specific mRNAs. The other model proposes that the two proteins function separately. Studying REGE-1, the Caenorhabditis elegans ortholog of Regnase-1, we have uncovered its functional relationship with RLE-1, the nematode counterpart of Roquin-1. While both proteins are essential for mRNA silencing, REGE-1 and RLE-1 appear to associate with target mRNA independently of each other. Thus, although the functional interdependence between REGE-1/Regnase-1 and RLE-1/Roquin-1 is conserved, the underlying mechanisms may display species-specific variation, providing a rare perspective on the evolution of this important post-transcriptional regulatory mechanism.

Ferritin is a unique buffering protein in iron metabolism. By storing or releasing iron in a tightly controlled manner, it prevents the negative effects of free ferrous ions on biomolecules in all domains of life – from bacteria to mammals. This review focuses on the structural features and activity of the ferritin protein family with an emphasis on nematode ferritins and the similarities in their biological roles with mammalian ferritins. The conservative characteristic of the ferritin family across the species originates from the ferroxidase activity against redox-active iron. The antioxidative function of these proteins translates into their involvement in a wide range of important biological processes, e.g., aging, fat metabolism, immunity, anticancer activity, and antipathogenic activity. Moreover, disturbances in ferritin expression lead to severe iron-associated diseases. Research on the Caenorhabditis elegans model organism may allow us to better understand the wide spectrum of mechanisms involving ferritin activity.

Bacterial regulatory RNAs require the chaperone protein Hfq to enable their pairing to mRNAs. Recent data showed that there is a hierarchy among sRNAs in the competition for access to Hfq, which could be important for the tuning of sRNA-dependent translation regulation. Here, seven structurally different sRNAs were compared using filter-based competition assays. Moreover, chimeric sRNA constructs were designed to identify structure elements important for competition performance. The data showed that besides the 3′-terminal oligouridine sequences also the 5′-terminal structure elements of sRNAs were essential for their competition performance. When the binding of sRNAs to Hfq mutants was compared, the data showed the important role of the proximal and rim sites of Hfq for the binding of six out of seven sRNAs. However, ChiX sRNA, which was the most efficient competitor, bound Hfq in a unique way using the opposite—distal and proximal—faces of this ring-shaped protein. The data indicated that the simultaneous binding to the opposite faces of Hfq was enabled by separate adenosine-rich and uridine-rich sequences in the long, single-stranded region of ChiX. Overall, the results suggest that the individual structural composition of sRNAs serves to tune their performance to different levels resulting in a hierarchy of sRNAs in the competition for access to the Hfq protein.