Journal Club – December 2019

Tubulin MRNA Degradation, Global Actin Flows, and Microtubule Plasticity

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TTC5 Mediates Autoregulation Of Tubulin Via mRNA Degradation

Lin et al. | Hegde Lab | Science

The soluble pool of tubulin monomers influences microtubule dynamics and microtubule-driven cellular processes including mitosis. As such, the cell imparts strict control over the concentration of soluble tubulin by selective degradation of tubulin mRNAs, a process known as tubulin autoregulation. In a November issue of Science, the Hegde lab reports new mechanistic details of tubulin mRNA degradation using a site-specific photo-crosslinking method. The authors identify TTC5, a highly conserved eukaryotic protein, as a critical ribosome-associating factor that specifically marks tubulin-translating ribosomes and triggers tubulin mRNA decay. Structural and mutagenesis methods further reveal that TTC5 recognizes and engages the first 4 amino acids of the nascent tubulin polypeptide as it emerges from the ribosome during translation. Overall, this study establishes a paradigm of co-translational protein regulation wherein mRNA degradation is specified by the encoded nascent polypeptide.

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