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Non-coding RNAs (ncRNAs) are involved in different cellular processes and some of them are considered to play a role in the development of numerous diseases. The recent discovery of ncRNAs is the result of several experimental and bioinformatics studies. On July 21-23, 2021, the 'Noncoding RNA World: From Mechanism to Therapy' conference that was held virtually (originally planned to be held in Basel, Switzerland), gathered experts and researchers from countries worldwide to cover the latest achievements in ncRNA research, including the basic molecular mechanisms and structural biology, bioinformatics, biotechnology, disease development and therapeutics of ncRNAs. The meeting was dominated by a feeling of satisfaction and enthusiasm for the novel discoveries in the ncRNA field that is considered to be relatively new. Intriguingly, several discoveries are added daily beside numerous hurdles that are encountered or remain to be resolved in order for these findings to be translated into clinical practice. [ABSTRACT FROM AUTHOR]

The lower convective layer (LCL) of the Atlantis II brine pool of the Red sea is a unique environment in terms of high salinity, temperature, and high concentrations of heavy metals. Mercuric reductase enzymes functional in such extreme conditions could be considered as a potential tool in the environmental detoxification of mercurial poisoning and might alleviate ecological hazards in the mining industry. Here, we constructed a mercuric reductase library from Atlantis II, from which we identified genes encoding two thermostable mercuric reductase (MerA) isoforms: one is halophilic (designated ATII-LCL) while the other is not (designated ATII-LCL-NH). The ATII-LCL MerA has a short motif composed of four aspartic acids (4D414-417) and two characteristic signature boxes that played a crucial role in its thermal stability. To further understand the mechanism behind the thermostability of the two studied enzymes, we mutated the isoform ATII-LCL-NH and found that the substitution of 2D at positions 415/416 enhanced the thermal stability, while other mutations had the opposite effect. The 2D mutant showed superior thermal tolerance as it retained 81% of its activity after 10 minutes incubation at 70°C. Three-dimensional structure prediction revealed newly formed salt-bridges and H-bonds in the 2D mutant, compared to the parent molecule. To the best of our knowledge, this study is the first to rationally design a mercuric reductase with enhanced thermal stability, which we propose to have a strong potential in bioremediation of mercurial poisoning. [ABSTRACT FROM AUTHOR]

Lysine specific demethylase-1 (LSD1) has been shown to be critical in acute myeloid leukemia (AML) pathogenesis and this has led to the development of LSD1 inhibitors (LSD1i) which are currently tested in clinical trials. Nonetheless, preclinical studies reported that AML cells frequently exhibit intrinsic resistance to LSD1 inhibition, and the molecular basis for this phenomenon is largely unknown. We explored the potential involvement of mammalian target of rapamycin (mTOR) in mediating the resistance of leukemic cells to LSD1i. Strikingly, unlike sensitive leukemias, mTOR complex 1 (mTORC1) signaling was robustly triggered in resistant leukemias following LSD1 inhibition. Transcriptomic, chromatin immunoprecipitation and functional studies revealed that insulin receptor substrate 1(IRS1)/extracellular-signal regulated kinases (ERK1/2) signaling critically controls LSD1i induced mTORC1 activation. Notably, inhibiting mTOR unlocked the resistance of AML cell lines and primary patient-derived blasts to LSD1i both in vitro and in vivo In conclusion, mTOR activation might act as a novel pro-survival mechanism of intrinsic as well as acquired resistance to LSD1i, and combination regimens co-targeting LSD1/mTOR could represent a rational approach in AML therapy., (Copyright© 2020 Ferrata Storti Foundation.)