ABSTRACT
Gene loss is a prevalent source of genetic variation in genome evolution. Calling loss events effectively and efficiently is a critical step for systematically characterizing their functional and phylogenetic profiles genome wide. Here, we developed a novel pipeline integrating orthologous inference and genome alignment. Interestingly, we identified 33 gene loss events that give rise to evolutionarily novel long noncoding RNAs (lncRNAs) that show distinct expression features and could be associated with various functions related to growth, development, immunity, and reproduction, suggesting loss relics as a potential source of functional lncRNAs in humans. Our data also demonstrated that the rates of protein gene loss are variable among different lineages with distinct functional biases.
Subject(s)
RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Gene Expression Profiling , Phylogeny , GenomeABSTRACT
Gene transcription and protein translation are two key steps of the 'central dogma.' It is still a major challenge to quantitatively deconvolute factors contributing to the coding ability of transcripts in mammals. Here, we propose ribosome calculator (RiboCalc) for quantitatively modeling the coding ability of RNAs in human genome. In addition to effectively predicting the experimentally confirmed coding abundance via sequence and transcription features with high accuracy, RiboCalc provides interpretable parameters with biological information. Large-scale analysis further revealed a number of transcripts with a variety of coding ability for distinct types of cells (i.e. context-dependent coding transcripts), suggesting that, contrary to conventional wisdom, a transcript's coding ability should be modeled as a continuous spectrum with a context-dependent nature.
Subject(s)
Models, Biological , Protein Biosynthesis , RNA , Transcription, Genetic , Animals , Genome, Human , Humans , Mammals/genetics , Mammals/metabolism , RNA/metabolism , RNA, Long Noncoding/genetics , Ribosomes/genetics , Ribosomes/metabolism , Transcription, Genetic/geneticsABSTRACT
Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.
Subject(s)
Neoplasm Recurrence, Local/genetics , Neoplasms/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Age Factors , Atlases as Topic , Humans , Molecular Sequence Annotation , Neoplasm Metastasis , Neoplasm Recurrence, Local/ethnology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasms/classification , Neoplasms/ethnology , Neoplasms/mortality , RNA, Long Noncoding/classification , RNA, Long Noncoding/metabolism , RNA, Messenger/classification , RNA, Messenger/metabolism , Racial Groups , Sex Factors , Survival AnalysisABSTRACT
With advances in next-generation sequencing technologies, numerous novel transcripts in a large number of organisms have been identified. With the goal of fast, accurate assessment of the coding ability of RNA transcripts, we upgraded the coding potential calculator CPC1 to CPC2. CPC2 runs â¼1000 times faster than CPC1 and exhibits superior accuracy compared with CPC1, especially for long non-coding transcripts. Moreover, the model of CPC2 is species-neutral, making it feasible for ever-growing non-model organism transcriptomes. A mobile-friendly web server, as well as a downloadable standalone package, is freely available at http://cpc2.cbi.pku.edu.cn.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, RNA/methods , Software , Algorithms , Animals , Gene Expression Profiling , Humans , Internet , Mice , RNA, Long Noncoding/chemistry , RNA, Messenger/chemistry , RNA, Small Untranslated/chemistryABSTRACT
In the endothelium, ROS mainly derive from mitochondria, endothelial nitric oxide synthases and NADPH oxidases 4. Excessive ROS are a major cause of oxidative stress, the primary stimulus of vascular dysfunction and oxidative stress-related diseases. However, cellular evolution has made possible the development of adaptive antioxidant systems that scavenge excessive ROS, such as Nrf2/Keapl-ARE, PPAR-y, SIRT and FOXO, etc. Among them, the Nrf2/Keapl-ARE signaling pathway is perhaps the most prominent. What is more, there are the "crosstalk" among these antioxidant stress-related signaling pathways aim to alleviate oxidative stress injurys and promote cells survival. The understanding of the relationship between endothelial aging and oxidative stress may serve as a therapeutic clues in the treatment of oxidative stress-related diseases.
