Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay

2024/11/17 by Alina Batiuk, Markus Höpfler, Ana C. Almeida +6 · 1 voice · 10 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced biosensing and bioanalysis techniques #Biochemistry #Biology #Cell #Cell biology #Cell division #Chemistry #Effector #Gene #Genomics and Chromatin Dynamics #Intracellular #Messenger RNA #Microtubule #Microtubule and mitosis dynamics #RNA #Ribosome #Tubulin

paper · doi:10.1038/s41467-024-54036-0

openalex publication_date 2024/11/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport, and power cell division. The concentration of αβ-tubulins is tightly controlled through a posttranscriptional mechanism involving selective and regulated degradation of tubulin-encoding mRNAs. Degradation is initiated by TTC5, which recognizes tubulin-synthesizing ribosomes and recruits downstream effectors to trigger mRNA deadenylation. Here, we investigate how cells regulate TTC5 activity. Biochemical and structural proteomic approaches reveal that under normal conditions, soluble αβ-tubulins bind to and sequester TTC5, preventing it from engaging nascent tubulins at translating ribosomes. We identify the flexible C-terminal tail of TTC5 as a molecular switch, toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss of sequestration by soluble αβ-tubulins constitutively activates TTC5, leading to diminished tubulin mRNA levels and compromised microtubule-dependent chromosome segregation during cell division. Our findings provide a paradigm for how cells regulate the activity of a specificity factor to adapt posttranscriptional regulation of gene expression to cellular needs.

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• Multilayered regulation of cytoskeletal protein abundance: autoregulatory mechanisms of actin and tubulin. [europepmc]
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• Tubulin autoregulation controls the biosynthesis of γ-tubulin to ensure mitotic fidelity [europepmc]

Discussions

• Hello Bluesky community! What a better way to introduce myself and my research team than post our lab’s first paper freshly off press 🥳🍾 We reveal how tubulins regulate the stability of their mRNA [bsky, 79 points, 1 comments]

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