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Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision

ABSTRACT: The fidelity of immune responses depends on a timely controlled and selective mRNA degradation that is largely driven by RNA-binding proteins (RBPs). It remains unclear whether the selection of an individual mRNA molecule for degradation is governed by stochastic or directed processes. Here, we show that tristetraprolin (TTP, also known as ZFP36), an essential anti-inflammatory RBP, destabilizes target mRNAs via a hierarchical molecular assembly. The formation of the assembly strictly relies on the interaction of TTP with RNA. The TTP homolog ZFP36L1 exhibits similar requirements, indicating a broader relevance of this regulatory program. Unexpectedly, the assembly of the cytoplasmic mRNA-destabilization complex is licensed in the nucleus by TTP binding to pre-mRNA, while cytoplasmic mRNA does not constitute a de novo TTP target. Hence, the fate of an inflammation-induced mRNA is decided concomitantly with its synthesis. This mechanism prevents the translation of excessive and potentially harmful inflammation mediators, irrespective of transcription.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: WeiQiang Chen

LAB HEAD: Pavel Kovarik

PROVIDER: PXD051662 | Pride | 2025-01-07

REPOSITORIES: Pride

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			Action	DRS
	20240123_E3_NEO7_vonWiren_Kovarik_MPL_UniWien_MPLID24010_s13_GFP_rep1_24c6p.raw	Raw
	20240123_E3_NEO7_vonWiren_Kovarik_MPL_UniWien_MPLID24010_s14_GFP_rep2_46p.raw	Raw
	20240123_E3_NEO7_vonWiren_Kovarik_MPL_UniWien_MPLID24010_s15_GFP_rep3_28c7p.raw	Raw
	20240123_E3_NEO7_vonWiren_Kovarik_MPL_UniWien_MPLID24010_s1_WT_rep1_35c5p.raw	Raw
	20240123_E3_NEO7_vonWiren_Kovarik_MPL_UniWien_MPLID24010_s2_WT_rep2_14c5p.raw	Raw

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Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision

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