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Science. 2019 Nov 14. pii: eaaz4352. doi: 10.1126/science.aaz4352. [Epub ahead of print]

TTC5 mediates autoregulation of tubulin via mRNA degradation.

Author information

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.

Abstract

Tubulins play crucial roles in cell division, intracellular traffic, and cell shape. Tubulin concentration is autoregulated by feedback control of mRNA degradation via an unknown mechanism. Here, we identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers co-translational degradation of tubulin mRNAs in response to excess soluble tubulin. Structural analysis revealed that TTC5 binds near the ribosome exit tunnel and engages the N 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.

PMID:
31727855
DOI:
10.1126/science.aaz4352

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