TTC5 mediates autoregulation of tubulin via mRNA degradation.

TTC5 mediates autoregulation of tubulin via mRNA degradation.

Science (New York, N.Y.) (2019-11-16)

Zhewang Lin, Ivana Gasic, Viswanathan Chandrasekaran, Niklas Peters, Sichen Shao, Timothy J Mitchison, Ramanujan S Hegde

PMID31727855

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.

MATERIALS

Product Number

Brand

Product Description

763705

Sigma-Aldrich

Graphene oxide, 2 mg/mL, dispersion in H₂O, avg. no. of layers, 1

F3165

Sigma-Aldrich

Monoclonal ANTI-FLAG^® M2, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)

A8592

Sigma-Aldrich

Monoclonal ANTI-FLAG^® M2-Peroxidase (HRP) antibody produced in mouse, clone M2, purified immunoglobulin, buffered aqueous glycerol solution