RESUMO
As an increasing number of noncoding RNAs (ncRNAs) have been suggested to encode short bioactive peptides in cancer, the exploration of ncRNA-encoded small peptides (ncPEPs) is emerging as a fascinating field in cancer research. To assist in studies on the regulatory mechanisms of ncPEPs, we describe here a database called SPENCER (http://spencer.renlab.org). Currently, SPENCER has collected a total of 2806 mass spectrometry (MS) data points from 55 studies, covering 1007 tumor samples and 719 normal samples. Using an MS-based proteomics analysis pipeline, SPENCER identified 29 526 ncPEPs across 15 different cancer types. Specifically, 22 060 of these ncPEPs were experimentally validated in other studies. By comparing tumor and normal samples, the identified ncPEPs were divided into four expression groups: tumor-specific, upregulated in cancer, downregulated in cancer, and others. Additionally, since ncPEPs are potential targets for neoantigen-based cancer immunotherapy, SPENCER also predicted the immunogenicity of all the identified ncPEPs by assessing their MHC-I binding affinity, stability, and TCR recognition probability. As a result, 4497 ncPEPs curated in SPENCER were predicted to be immunogenic. Overall, SPENCER will be a useful resource for investigating cancer-associated ncPEPs and may boost further research in cancer.
Assuntos
Bases de Dados Genéticas , Bases de Dados de Proteínas , Neoplasias/genética , Peptídeos/genética , Humanos , Espectrometria de Massas , RNA não Traduzido/genética , SoftwareRESUMO
The insulin signalling pathway plays a crucial role in regulating the metabolism of sugars, fats and proteins in cells, thereby affecting the growth, metabolism, reproduction and ageing of organisms. However, little is known about the functions of long non-coding RNAs (lncRNAs) in the regulation of insulin receptors under stress conditions in insects. In this study, we showed that insulin receptor-associated lncRNA (IRAR) regulates insulin receptor transcripts in response to nutritional stress in Drosophila melanogaster. Genome editing by CRISPR-Cas9 showed reduced sensitivity of IRAR mutants to environmental nutritional changes. In contrast, the sensitivity of mutants overexpressing tubulin-gal4 > IRAR increased under low nutrition. The pupation and eclosion timings in IRAR mutants were significantly delayed with an increase in insulin concentration compared with that in the w1118 group. In addition, the expression pattern of IRAR was almost consistent with that of the four transcripts of the insulin receptor from the embryonic period to the adult period. RNA immunoprecipitation assay showed the direct regulation of insulin receptor transcripts by IRAR to the through FOXO binding under nutritional stress. To our knowledge, this is the first study that describes a model of lncRNA-mediated development regulation through insulin receptor transcripts.
Assuntos
Proteínas de Drosophila , RNA Longo não Codificante , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Insulina/genética , Insulina/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismoRESUMO
Ribosome biogenesis and processing involve the coordinated action of many components. The DEAD-box RNA helicase (Rok1) is essential for cell viability, and the depletion of Rok1 inhibits pre-rRNA processing. Previous research on Rok1 and its cofactor Rrp5 has been performed primarily in yeast. Few functional studies have been performed in complex multicellular eukaryotes. Here, we used a combination of genetics and developmental experiments to show that Rok1 and Rrp5, which localize to the nucleolus, play key roles in the pre-rRNA processing and ribosome assembly in D. melanogaster. The accumulation of pre-rRNAs caused by Rok1 depletion can result in developmental defects. The loss of Rok1 enlarged the nucleolus and led to stalled ribosome assembly and pre-rRNA processing in the nucleolus, thereby blocking rRNA maturation and exacerbating the inhibition of mitosis in the brain. We also discovered that rrp54-2/4-2 displayed significantly increased ITS1 signaling by fluorescence in situ hybridization, and a reduction in ITS2. Rrp5 signal was highly enriched in the core of the nucleolus in the rok1167/167 mutant, suggesting that Rok1 is required for the accurate cellular localization of Rrp5 in the nucleolus. We have thus uncovered functions of Rok1 that reveal important implications for ribosome processing in eukaryotes.