人类 TREM2 5'非翻译区的翻译调控和蛋白编码能力。

Translational regulation and protein-coding capacity of the 5' untranslated region of human TREM2.

机构信息

Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi, Tokyo, 204-8588, Japan.

Department of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi, Tokyo, 204-8588, Japan.

出版信息

Commun Biol. 2023 Jun 8;6(1):616. doi: 10.1038/s42003-023-04998-6.

DOI:10.1038/s42003-023-04998-6

PMID:37291187

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10250343/

Abstract

TREM2 is a transmembrane receptor expressed in microglia and macrophages. Elevated TREM2 levels in these cells are associated with age-related pathological conditions, including Alzheimer's disease. However, the regulatory mechanism underlying the protein expression of TREM2 remains unclear. In this study, we uncover the role of the 5' untranslated region (5'-UTR) of human TREM2 in translation. An upstream start codon (uAUG) in the 5'-UTR of TREM2 is specific to some primates, including humans. The expression of the conventional TREM2 protein, starting from the downstream AUG (dTREM2), is repressed by the 5'-UTR in a uAUG-mediated manner. We also detect a TREM2 protein isoform starting from uAUG (uTREM2) that is largely degraded by proteasomes. Finally, the 5'-UTR is essential for the downregulation of dTREM2 expression in response to amino acid starvation. Collectively, our study identifies a species-specific regulatory role of the 5'-UTR in TREM2 translation.

摘要

TREM2 是一种表达于小胶质细胞和巨噬细胞的跨膜受体。这些细胞中 TREM2 水平的升高与年龄相关的病理状况有关，包括阿尔茨海默病。然而，TREM2 蛋白表达的调节机制尚不清楚。在这项研究中，我们揭示了人类 TREM2 的 5'非翻译区（5'-UTR）在翻译中的作用。TREM2 的 5'-UTR 中有一个上游起始密码子（uAUG），仅存在于某些灵长类动物，包括人类中。从下游 AUG（dTREM2）开始表达的常规 TREM2 蛋白受到 uAUG 介导的 5'-UTR 的抑制。我们还检测到一种从 uAUG 开始的 TREM2 蛋白异构体（uTREM2），它主要被蛋白酶体降解。最后，5'-UTR 对于氨基酸饥饿时 dTREM2 表达的下调是必需的。总之，我们的研究确定了 5'-UTR 在 TREM2 翻译中具有种特异性的调节作用。