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FEM1B 终止密码子通读调控人科特异性细胞周期。

Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B.

机构信息

Department of Biochemistry, Indian Institute of Science, Bengaluru 560012, India.

Undergraduate Program, Indian Institute of Science, Bengaluru 560012, India.

出版信息

J Cell Sci. 2024 Aug 15;137(16). doi: 10.1242/jcs.261921. Epub 2024 Aug 29.

DOI:10.1242/jcs.261921
PMID:39140134
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11385324/
Abstract

FEM1B is a substrate-recognition component of the CRL2 E3 ubiquitin-protein ligase. This multi-protein complex targets specific proteins for ubiquitylation, which leads to their degradation. Here, we demonstrate the regulation of FEM1B expression by stop codon readthrough (SCR). In this process, translating ribosomes readthrough the stop codon of FEM1B to generate a C-terminally extended isoform that is highly unstable. A total of 81 nucleotides in the proximal 3'UTR of FEM1B constitute the necessary and sufficient cis-signal for SCR. Also, they encode the amino acid sequence responsible for the degradation of the SCR product. CRISPR-edited cells lacking this region, and therefore SCR of FEM1B, showed increased FEM1B expression. This in turn resulted in reduced expression of SLBP (a target of FEM1B-mediated degradation) and replication-dependent histones (target of SLBP for mRNA stability), causing cell cycle delay. Evolutionary analysis revealed that this phenomenon is specific to the genus Pan and Homo (Hominini). Overall, we show a relatively recently evolved SCR process that relieves the cell cycle from the negative regulation by FEM1B.

摘要

FEM1B 是 CRL2 E3 泛素蛋白连接酶的底物识别组件。该多蛋白复合物将特定蛋白质靶向进行泛素化，导致其降解。在这里，我们证明了 FEM1B 表达受终止密码子通读 (SCR) 的调节。在此过程中，翻译核糖体通读 FEM1B 的终止密码子，产生 C 端延伸的异构体，其极不稳定。FEM1B 近端 3'UTR 中的总共 81 个核苷酸构成 SCR 的必要和充分的顺式信号。此外，它们编码负责 SCR 产物降解的氨基酸序列。缺乏该区域的 CRISPR 编辑细胞，因此 FEM1B 的 SCR 缺失，导致 FEM1B 表达增加。这反过来又导致 SLBP（FEM1B 介导降解的靶标）和复制依赖性组蛋白（SLBP 用于 mRNA 稳定性的靶标）的表达减少，导致细胞周期延迟。进化分析表明，这种现象是特定于 Pan 和 Homo 属（Hominini）的。总的来说，我们展示了一种相对较新进化的 SCR 过程，该过程使细胞周期摆脱了 FEM1B 的负调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/5018146b3dd9/joces-137-261921-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/68689e178daf/joces-137-261921-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/f5933b20057b/joces-137-261921-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/a22cf8d2fad8/joces-137-261921-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/96a9cc487103/joces-137-261921-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/7a6fdb458323/joces-137-261921-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/f7993e631b10/joces-137-261921-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/b46c8a2c9126/joces-137-261921-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/5018146b3dd9/joces-137-261921-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/68689e178daf/joces-137-261921-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/f5933b20057b/joces-137-261921-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/a22cf8d2fad8/joces-137-261921-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/96a9cc487103/joces-137-261921-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/7a6fdb458323/joces-137-261921-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/f7993e631b10/joces-137-261921-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/b46c8a2c9126/joces-137-261921-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd4/11385324/5018146b3dd9/joces-137-261921-g8.jpg

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2
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7
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