TTC5 mediates autoregulation of tubulin via mRNA degradation.
basic_science · Level V
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- Record sourced from PubMed, PMID 31727855.
- Also identified by DOI 10.1126/science.aaz4352 and PMC identifier 6942541.
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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.
Medical subject headings
- Feedback, Physiological
- RNA Stability
- RNA, Messenger
- Ribosomes
- Transcription Factors
- Tubulin