An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development

Yang, Ying; Wang, Yan; Zhang, Yuanliang; Chen, Lei; Chen, Gennong; Bao, Zhaoshi; Yang, Yang; Xie, Zhi; Zhao, Qian

doi:10.1016/j.mcpro.2022.100480

Cited by 4 publications

(4 citation statements)

References 64 publications

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“…However, after birth, hepatocytes must acquire the proper repertoire of proteins that both enable them to survive ex utero and assume mature liver functions that are vital for the life of the organism. For instance, sequential changes in alternative splicing in the postnatal period help generate new proteoforms to support hepatocyte maturity 14,87 .…”

Section: Discussionmentioning

confidence: 99%

ESRP2-microRNA-122 axis directs the postnatal onset of liver polyploidization and maturation

Bangru,

Chen,

Baker

et al. 2024

Preprint

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SUMMARYHepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intra- and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of Epithelial-Splicing-Regulatory-Protein-2 (ESRP2) stimulates biogenesis of liver-specific microRNA (miR-122), thereby facilitating polyploidization, maturation, and functional competence of hepatocytes. By determining transcriptome-wide protein-RNA interactionsin vivoand integrating them with single-cell and bulk hepatocyte RNA-seq datasets, we delineate an ESRP2-driven RNA processing program that drives sequential replacement of fetal-to-adult transcript isoforms. Specifically, ESRP2 binds the primary miR-122 host gene transcript to promote its processing/biogenesis. Combining constitutive and inducible ESRP2 gain- and loss-of-function mice models with miR-122 rescue experiments, we demonstrate that timed activation of ESRP2 augments miR-122-driven program of cytokinesis failure, ensuring proper onset and extent of hepatocyte polyploidization.

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Section: Discussionmentioning

confidence: 99%

ESRP2-microRNA-122 axis directs the postnatal onset of liver polyploidization and maturation

Bangru,

Chen,

Baker

et al. 2024

Preprint

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show abstract

Section: Methodsmentioning

confidence: 99%

“…For the HCD experiments, the samples were analyzed using Q Exactive Plus with an EASY-spray source and EASY-nLC 1200 system (Thermo Fisher Scientific) or Orbitrap Exploris 480 (Thermo Fisher Scientific) equipped with an EASY-spray source and a Dionex UltiMate 3000 LC system (Thermo Fisher Scientific). 37 The instrument was operated in data-dependent mode. With the EASY-nLC system, 6 μL of sample was loaded onto a 25 cm EASY-SPRAY column (Thermo Fisher Scientific), a gradient from 3% to 45% solvent B (80% acetonitrile with 0.1% formic acid) was run from 0 to 75 min, followed by 15 min column wash-off at 100% B with a total of 90 min per run.…”

Section: Liquid Chromatography-mass Spectrometry (Lc-ms) For Glycopro...mentioning

confidence: 99%

Comprehensive Glycomic and Glycoproteomic Analyses of Human Programmed Cell Death Protein 1 Extracellular Domain

Chen,

Tan,

Tang

et al. 2024

J. Proteome Res.

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Human programmed cell death protein 1 (hPD-1) is an essential receptor in the immune checkpoint pathway. It has played an important role in cancer therapy. However, not all patients respond positively to the PD-1 antibody treatment, and the underlying mechanism remains unknown. PD-1 is a transmembrane glycoprotein, and its extracellular domain (ECD) is reported to be responsible for interactions and signal transduction. This domain contains 4 N-glycosylation sites and 25 potential O-glycosylation sites, which implicates the importance of glycosylation. The structure of hPD-1 has been intensively studied, but the glycosylation of this protein, especially the glycan on each glycosylation site, has not been comprehensively illustrated. In this study, hPD-1 ECD expressed by human embryonic kidney 293 (HEK 293) and Chinese hamster ovary (CHO) cells was analyzed; not only N-and O-glycosylation sites but also the glycans on these sites were comprehensively analyzed using mass spectrometry. In addition, hPD-1 ECD binding to different anti-hPD-1 antibodies was tested, and N-glycans were found functioned differently. All of this glycan information will be beneficial for future PD-1 studies.

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“…Some of the most commonly used methods for microprotein enrichment include solid-phase extraction, urea-tricine polyacrylamide gel electrophoresis (PAGE), acid precipitation, and molecular weight cut-off (MWCO) filtration. 34 , 36 These methods have resulted in the identification of several microproteins, 37 , 38 , 39 , 40 and when combined with sequencing-based or bioinformatic approaches, they may be the most robust approach for high confidence microprotein discovery and identification. 34 This was recently highlighted with the implementation of comprehensive proteogenomic approaches combining peptidomics and RNA sequencing to filter out known peptides and exclusively identify new microproteins.…”

Section: Tools and Methods For Microprotein Discoverymentioning

confidence: 99%

Microproteins: Overlooked regulators of physiology and disease

2023

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An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development

Cited by 4 publications

References 64 publications

ESRP2-microRNA-122 axis directs the postnatal onset of liver polyploidization and maturation

ESRP2-microRNA-122 axis directs the postnatal onset of liver polyploidization and maturation

Comprehensive Glycomic and Glycoproteomic Analyses of Human Programmed Cell Death Protein 1 Extracellular Domain

Microproteins: Overlooked regulators of physiology and disease

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