Quantitative Proteomics Identifies Profilin-1 As a Pseudouridine-Binding Protein

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Date 2025 Jan 15

PMID 39812085

Authors

Songbo Wei

Xiaoxia Dai

Jun Yuan

Shiyang He

Kriti Shah

Shiyuan Guo

Zheng Duan

Jernej Murn

Yinsheng Wang

Affiliations

Soon will be listed here.

Abstract

Pseudouridine (Ψ) is the most abundant RNA modification in nature; however, not much is known about the biological functions of this modified nucleoside. Employing an unbiased quantitative proteomics method, we identified multiple candidate reader proteins of Ψ in RNA, including a cytoskeletal protein profilin-1 (PFN1). We demonstrated that PFN1 binds directly and selectively to Ψ-containing RNA. Additionally, we discovered approximately 4000 binding sites of PFN1 in human cells, including a known dyskerin (DKC1)-installed Ψ site in mRNA, which encodes triosephosphate isomerase. Moreover, we showed that PFN1 and DKC1 are crucial for regulating the stability and translation efficiency of mRNA through modulating PFN1-Ψ interaction. Together, we identified PFN1 as a reader protein of Ψ in RNA and illustrated a potential role of PFN1-Ψ interaction in post-transcriptional regulation. These findings provide new insights into the functions of Ψ in RNA biology and in modulating the expression of an important metabolic enzyme.

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