Akhtar, MN and Singh, A and Manjunath, LE and Dey, D and Kumar, SD and Vasu, K and Das, A and Eswarappa, SM (2024) Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B. In: Journal of Cell Science, 137 (16).
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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. © 2024. Published by The Company of Biologists Ltd.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Cell Science |
| Publisher: | Company of Biologists Ltd |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | cell cycle protein; cleavage and polyadenylation specificity factor; histone; messenger RNA; nuclear protein; SLBP protein, human, 3' untranslated region; animal; cell cycle; genetics; HEK293S cell line; human; metabolism; protein synthesis; stop codon, 3' Untranslated Regions; Animals; Cell Cycle; Cell Cycle Proteins; Codon, Terminator; HEK293 Cells; Histones; Humans; mRNA Cleavage and Polyadenylation Factors; Nuclear Proteins; Protein Biosynthesis; RNA, Messenger |
| Department/Centre: | Division of Biological Sciences > Biochemistry UG Programme |
| Date Deposited: | 25 Sep 2024 09:08 |
| Last Modified: | 25 Sep 2024 09:08 |
| URI: | http://eprints.iisc.ac.in/id/eprint/86270 |
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