2. Academic Validation
  3. TTC5 mediates autoregulation of tubulin via mRNA degradation

TTC5 mediates autoregulation of tubulin via mRNA degradation

  • Science. 2020 Jan 3;367(6473):100-104. doi: 10.1126/science.aaz4352.
Zhewang Lin 1,  Ivana Gasic 2,  Viswanathan Chandrasekaran 1,  Niklas Peters 1,  Sichen Shao 3,  Timothy J Mitchison 2,  Ramanujan S Hegde 4
Affiliations

Affiliations

  • 1 MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • 2 Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • 3 Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • 4 MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. rhegde@mrc-lmb.cam.ac.uk.
PMID: 31727855 DOI: 10.1126/science.aaz4352
Abstract

Tubulins play crucial roles in cell division, intracellular traffic, and cell shape. Tubulin concentration is autoregulated by feedback control of messenger RNA (mRNA) degradation via an unknown mechanism. We identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers cotranslational degradation of tubulin mRNAs in response to excess soluble tubulin. Structural analysis revealed that TTC5 binds near the ribosome exit tunnel and engages the amino terminus of nascent tubulins. TTC5 mutants incapable of ribosome or nascent tubulin interaction abolished tubulin autoregulation and showed chromosome segregation defects during mitosis. Our findings show how a subset of mRNAs can be targeted for coordinated degradation by a specificity factor that recognizes the nascent polypeptides they encode.

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