The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells. TRINGS binds to STRAP and inhibits STRAP-GSK3b-NF-jB necrotic signaling to protect tumor cells from cell death. Interestingly, TRINGS appears to respond to glucose starvation specifically, as it is not activated by serum, serine, or glutamine deprivation. Collectively, our findings reveal that p53-induced lncRNA TRINGS controls the necrotic pathway and contributes to the survival of cancer cells harboring wild-type p53 under glucose stress.
The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness. We recruited 92 consanguineous families segregating stable or progressive, recessively inherited moderate or severe hearing loss. We utilized homozygosity mapping, Sanger sequencing, targeted capture of known deafness genes with massively parallel sequencing and whole exome sequencing to identify the molecular basis of hearing loss in these families. Variants of the known deafness genes were found in 69% of the participating families with the SLC26A4, GJB2, MYO15A, TMC1, TMPRSS3, OTOF, MYO7A and CLDN14 genes together accounting for hearing loss in 54% of the families. We identified 20 reported and 21 novel variants in 21 known deafness genes. Sixteen of the twenty reported variants, previously associated with stable, profound deafness were associated with moderate to severe or progressive hearing loss in our families. These data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity.
Long non-coding RNAs (lncRNAs) are critical in the regulation of various biological processes. In recent years, plethora of lncRNAs have been identified in mammalian genomes through different approaches, and the researchers are constantly reporting the regulatory roles of these lncRNAs, which leads to complexity of literature about particular lncRNAs. Therefore, for the convenience of the researchers, we collected regulatory relationships of the lncRNAs and built a database called ‘LncReg’. This database is developed by collecting 1081 validated lncRNA-associated regulatory entries, including 258 non-redundant lncRNAs and 571 non-redundant genes. With regulatory relationships information, LncReg can provide overall perspectives of regulatory networks of lncRNAs and comprehensive data for bioinformatics research, which is useful for understanding the functional roles of lncRNAs.Database URL: http://bioinformatics.ustc.edu.cn/lncreg/
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