de-novo-identification-actively-translated-open-reading-frames-with

<em>De novo</em> Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Identification of open reading frames (ORFs), especially those encoding small peptides and being actively translated under specific physiological ...

Xi’an Jiaotong University Health Science Center

Chromatin and associated epigenetic marks provide important platforms for gene regulation in response to metabolic changes associated with environmental exposures, including physiological stress, nutritional deprivation, and starvation. Numerous studies have shown that fluctuations of key metabolites can influence chromatin modifications, but their effects on chromatin structure (e.g. chromatin compaction, nucleosome arrangement, and chromatin loops) and how they appropriately deposit specific chemical modification on chromatin are largely unknown. Here, focusing on methionine metabolism, we discuss recent developments of metabolic effects on chromatin modifications and structure, as well as consequences on gene regulation.

Epigenomic links from metabolism-methionine and chromatin architecture.

Aging has long been thought to be a major risk factor for various types of cancers. However, accumulating evidence indicates increased resistance of old animals to tumor growth. An in-depth understanding of how old individuals defend against tumor invasion requires further investigations.

Single-cell sequencing reveals antitumor characteristics of intratumoral immune cells in old mice.

Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation. The cooperation of spliced XBP1 and STAT3 reinforced the pro-tumorigenic phenotype and expression of immunosuppressive genes. Ablation of XBP1 expression with genetic manipulation or ameliorating ER stress responses by facilitating LPCAT3-mediated incorporation of unsaturated lipids to the phosphatidylcholine hampered pro-tumorigenic phenotype and survival in TAMs. Together, we uncover the unexpected roles of tumor-cell-produced lipids that simultaneously orchestrate macrophage polarization and survival in tumors via induction of ER stress responses and reveal therapeutic targets for sustaining host antitumor immunity.

Zhengtao Xiao

School of Basic Medical Sciences

Xi’an Jiaotong University Health Science Center

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Zhengtao Xiao

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Xi’an Jiaotong University Health Science Center

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

School of Basic Medical Sciences