Mammalian splicing divergence is shaped by drift, buffering in <i>trans</i>, and a scaling law

Zou, Xudong; Schaefke, Bernhard; Jia, Fujian; Sun, Wei; Li, Guipeng; Liang, Weizheng; Reif, Tristan; Heyd, Florian; Gao, Qingsong; Tian, Shuye; Li, Yanping; Tang, Yisen; Fang, Liang; Hu, Yuhui; Chen, Wei

doi:10.26508/lsa.202101333

Cited by 3 publications

(2 citation statements)

References 53 publications

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“…Pre-mRNA is spliced into mature mRNA by the spliceosome, and the mature RNA can be further translated into protein [ 31 , 32 ]. Different types of cells can produce different splicing variants through variable splicing [ 33 , 34 ]. Therefore, we next analyzed the differentially splicing genes (DSGs) between goose myoblast and myotube ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Sequencing Reveals Pathways Related to Proliferation and Differentiation of Shitou Goose Myoblasts

Chen

Zhang

Geng-Hua

et al. 2022

Animals

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Chinese Shitou goose is a type of large goose with high meat yield. Understanding the genetic regulation of muscle development in Shitou goose would be beneficial to improve the meat production traits of geese. Muscle development is regulated by genes related to myoblast proliferation and differentiation. In this study, the RNA-seq method was used to construct the mRNA and lncRNA expression profiles of Shitou goose myoblasts and myotubes. A total of 1664 differentially expressed (DE) mRNAs and 244 DE-lncRNAs were identified. The alternative mRNA splicing in proliferation and differentiation stages was also analyzed. Notably, pathways enriched in DE-mRNAs, DE-splicing transcripts, and DE-lncRNAs all point to the Wnt signaling pathway, indicating that the Wnt signaling is a key regulatory pathway of muscle development in Shitou goose. We also constructed the interactive network of DE-lncRNAs and DE-mRNAs and revealed some key genes of lncRNAs regulating the proliferation and differentiation of myoblasts. These results provide new insights for the study of the muscle development of the Shitou goose.

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Section: Resultsmentioning

confidence: 99%

Transcriptome Sequencing Reveals Pathways Related to Proliferation and Differentiation of Shitou Goose Myoblasts

Chen

Zhang

Geng-Hua

et al. 2022

Animals

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“…Instead, highly expressed alleles have actually relatively fewer additional isoforms than one would expect at that expression level, indicating a rather strict control of splicing efficiency. Hence, highly expressed loci, which are often also evolutionary old genes, appear to be less sensitive to the influence of noise, probably because their trans-regulation has been optimized 42 . This would also explain why they can maintain on average more splice variants than low expressed, evolutionarily younger genes.…”

Section: Discussionmentioning

confidence: 99%

Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations

Zhang,

Guenther,

Gao

et al. 2024

Preprint

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Most eukaryotic genes are expressed in multiple RNA isoforms representing variants of the respective genes. Full-length RNA sequencing techniques have uncovered an extreme diversity of RNA isoforms, but a subset of them might be generated by noise in the splicing machinery. For some genes, it has been shown that environmental influences can lead to isoform switching, implying that isoform diversity could also be subject to plastic changes in response to environmental conditions. Further, it has been suggested that isoform diversity could be a basis for adaptive evolutionary novelty. However, explicit tests of all three of these assumptions are missing. To address these questions, we have analyzed here the variation of full-length brain RNA transcripts from natural populations and subspecies ofMus musculus, as well as the outgroup speciesMus spretusandMus spicilegus. We find a substantial influence of splicing noise in generating rare isoform variants. However, after filtering these out, we reliably identify more than 117,000 distinct isoforms in the dataset, about doubling the number of the currently annotated set. Comparisons with individuals raised under different environmental conditions show a very strong plasticity effect in shaping isoform expression, including major isoform switching in proteins that bind to splice site enhancers. Using site frequency spectra tests in comparison to SNP data from the same individuals, we find no evidence for lineage-specific isoforms to become frequently fixed. We conclude that lineage-specific isoforms do not contribute much to novel adaptations, either because they are generated mainly through noise in the splicing machinery or are subject to negative selection. However, isoform diversity is strongly shaped by environmental conditions, both for lineage-specific isoforms, as well as conserved ones. Therefore, the functional role of isoform diversity may mostly be related to trigger plastic responses to environmental changes.

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Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis

Chen

Liang

et al. 2022

J Transl Med

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Background Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis. Methods A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules. Results Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log2 fold change| > 1.5, adjusted P value < 0.05 and variable importance in the projection (VIP) > 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the derivation results (area under the receiver operating characteristic curve (AUROC): 0.81–0.96/0.62–1.00). The pentose phosphate pathway was found to be related to sepsis-associated encephalopathy. Phenylalanine metabolism was associated with sepsis-associated acute kidney injury. The key molecular alterations of the multiomics network in sepsis compared to normal controls implicate acute inflammatory response, platelet degranulation, myeloid cell activation involved in immune response and phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis. Conclusions Integrated analysis of untargeted metabolomics and proteomics revealed characteristic metabolite and protein alterations in sepsis, which were mainly involved in inflammation-related pathways and amino acid metabolism. This study depicted the pathological characteristics and pathways involved in sepsis and potential therapeutic targets.

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Mammalian splicing divergence is shaped by drift, buffering in trans, and a scaling law

Cited by 3 publications

References 53 publications

Transcriptome Sequencing Reveals Pathways Related to Proliferation and Differentiation of Shitou Goose Myoblasts

Transcriptome Sequencing Reveals Pathways Related to Proliferation and Differentiation of Shitou Goose Myoblasts

Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations

Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis

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