YIPFα1A expression is regulated by multilayered molecular mechanisms

FEBS Open Bio

卷:16

Research Article

Tokio Takaji^1,2  Yurika Nakanishi¹  Nobuhiro Nakamura¹ 

[1] Division of Life Sciences, Graduate School of Kyoto Sangyo University, Japan

[2] CRIA, Kyoto University, Japan

关键词: 3′ untranslated region;    codon adaptation index;    Golgi;    mRNA stability;    translation;    transmembrane protein;   

DOI  :  10.1002/2211-5463.70244

 received in 2025-09-20, accepted in 2026-03-26,  发布年份 2026

来源: Wiley

【 摘 要 】

Yip domain family (YIPF) proteins are five‐pass transmembrane proteins that localize primarily to the Golgi apparatus. These proteins assemble into higher‐order complexes with each α‐subunit pairing specifically with a β‐subunit to form a dimer which then assemble into complexes with two to four dimers. Notably, β‐subunit expression depends on the corresponding α‐subunit partner, and conventional transient overexpression of α‐subunits has been extremely inefficient, hindering deeper analysis of YIPF complexes. To identify the cause of poor exogenous expression, we examined YIPF gene features and found two properties correlated with low expression: (i) rare‐codon enrichment in the CDS and (ii) extended 3′ UTRs. Experimental analyses focusing on YIPFα1A revealed that rare‐codon enrichment suppresses expression mainly at the mRNA level, consistent with translation‐coupled mRNA decay, whereas inclusion of the native 3′ UTR enhances expression by increasing mRNA abundance. Deletion mapping further showed that a proximal 3′ UTR segment (51–150) is necessary and sufficient for mRNA stabilization, thereby elevating both mRNA and protein levels. Conversely, a distal 3′ UTR fragment (1116–2230) increased mRNA but not protein levels, suggesting translational repression resulting in a reduced protein‐to‐mRNA ratio. Together, these findings explain the discrepancy between endogenous and exogenous YIPFα1A expression and propose a multilayered regulatory model in which rare codons decrease mRNA, the proximal 3′ UTR stabilizes mRNA, and the distal 3′ UTR reduces translation.Impact statementOur work advances YIPF biology and identifies post‑transcriptional mechanisms governing multi‑pass membrane proteins. We show rare‑codon and 3′ UTR‑based control of trafficking proteins—an area largely unexplored—and introduce a new paradigm for membrane‑traffic regulation that will guide future studies of complex assembly, localization, and homeostasis.

【 授权许可】

CC BY   
© 2026 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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