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Dynamic interactions of RNA binding proteins to human cytokine mRNA govern T cell responses

ABSTRACT: Effective T cell responses against infections and tumors depend on the production of effector molecules, including the key pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Recent studies revealed that post-transcriptional events determine the magnitude and duration of cytokine production in T cells, a feature that is largely defined by RNA-binding proteins (RBPs). However, to date the interplay of RBPs with cytokine mRNA, and their mode of action are ill-defined. Here we employed an RNA-aptamer-based capture assay from human T cell lysates to map RBP interactions with the full length 3’untranslated regions of IFNG, TNF and IL2. We found that RBPs binding can be both promiscuous and cytokine-specific. Furthermore, the RBP binding landscape rapidly alters upon T cell activation. Genetic deletion of confirmed mRNA interactors uncovered RBP-specific activity in primary T cells in response to target cells. Thus, RBPs are critical determinants of fast but tightly controlled cytokine production in T cells.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Floris van Alphen

LAB HEAD: Prof.Dr. A.B. Meijer

PROVIDER: PXD028171 | Pride | 2023-04-20

REPOSITORIES: Pride

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	EV_PMAIono_1.raw	Raw
	EV_PMAIono_2.raw	Raw

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