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.

• MeSH
• lidé MeSH
• messenger RNA * metabolismus   genetika   MeSH
• mikrotubuly * metabolismus   MeSH
• proteiny asociované s mikrotubuly metabolismus   genetika   MeSH
• ribozomy metabolismus   MeSH
• segregace chromozomů MeSH
• stabilita RNA * MeSH
• tubulin * metabolismus   genetika   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA * MeSH
• proteiny asociované s mikrotubuly MeSH
• tubulin * MeSH

Hundreds of mitochondrial proteins with N-terminal presequences are translocated across the outer and inner mitochondrial membranes via the TOM and TIM23 complexes, respectively. How translocation of proteins across two mitochondrial membranes is coordinated is largely unknown. Here, we show that the two domains of Tim50 in the intermembrane space, named core and PBD, both have essential roles in this process. Building upon the surprising observation that the two domains of Tim50 can complement each other in trans, we establish that the core domain contains the main presequence-binding site and serves as the main recruitment point to the TIM23 complex. On the other hand, the PBD plays, directly or indirectly, a critical role in cooperation of the TOM and TIM23 complexes and supports the receptor function of Tim50. Thus, the two domains of Tim50 both have essential but distinct roles and together coordinate translocation of proteins across two mitochondrial membranes.

• MeSH
• mitochondriální importní komplex MeSH
• mitochondriální membrány * metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny * metabolismus   MeSH
• transportní proteiny mitochondriální membrány genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mitochondriální importní komplex MeSH
• Saccharomyces cerevisiae - proteiny * MeSH
• transportní proteiny mitochondriální membrány MeSH