Dataset Information

Proteogenomic Profiling Reveals Functional Microproteins in T Cells

ABSTRACT: Noncanonical micropeptides, i.e., polypeptides mostly under 10 kDa, are encoded by genomic sequences that have been previously annotated as noncoding but now known as small open reading frames (sORFs). The recent identification of microproteins encoded by sORFs has provided evidence that many sORFs encode functional microproteins that play crucial roles in various biological processes. T cell activation is a critical biological process for adaptive immune response. Understanding key players in this process will allow us to decipher the complex mechanisms as well as develop immunotherapy for treating a wide range of diseases. Although there have been extensive studies on canonical proteins in T cell activation, the microproteins in T cells and their roles have been uncharted water to date. In this study, we combined nascent proteomics and quantitative proteomics to identify 411 novel microproteins in primary human T cells, including 83 nascent microproteins that are defined as newly synthesized polypeptides emerged during the translation of mRNA. We activated the T cell function with either PMA/Ionomycin (distal activation) or CD3/CD28 activating antibodies (proximal activation), and obtained a comprehensive canonical protein and microprotein profiles to pinpoint common and distinct differentially expressed proteins under these two activation conditions. After experimental testing, three microproteins numbered T1, T2 and T3 were found to be functional in regulating T cell activation. Bioinformatic and proteomic analyses suggested that T1 was functional related to immune as negative feedback to T cell activation. Our study not only established an integrated approach to uncover and elucidate novel microproteins but also highlight the significant role of microproteins in regulating T cell activation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture, Jurkat Cell

DISEASE(S): Lymphoma

SUBMITTER: Tianyang Zhu

LAB HEAD: Yang Yang

PROVIDER: PXD058995 | Pride | 2025-08-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20221219_TCell_TMT_Frac.mzML	Mzml
	20221219_TCell_TMT_Frac.mzid.gz	Mzid
	20221219_TCell_TMT_Frac1.raw	Raw
	20221219_TCell_TMT_Frac10.raw	Raw
	20221219_TCell_TMT_Frac2.raw	Raw

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Publications

Proteogenomics Reveals Microproteins in Activated T Cells.

Yang Yang Y Chen Chuangmiao C Li Kecheng K Zhang Yuanliang Y Chen Lei L Shi Jue J Mu Quanhua Q Xu Yang Y Zhao Qian Q

Molecular & cellular proteomics : MCP 20250204 6

Noncanonical micropeptides, or called novel microproteins, i.e., polypeptides mostly under 10 kDa, are encoded by genomic sequences that have been previously annotated as noncoding but now known as small open reading frames (sORFs). The recent identification of microproteins encoded by sORFs has provided evidence that many sORFs encode functional microproteins that play crucial roles in various biological processes. T cell activation is a critical biological process for adaptive immune response. ...[more]

PMID: 39914663

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