TTC5 mediates autoregulation of tubulin via mRNA degradation

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

doi:10.1126/science.aaz4352

TTC5 mediates autoregulation of tubulin via mRNA degradation

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

Biochemistry and Cell Biology

Stony Brook University

Medical Research Council
Harvard University
Heidelberg University

Research output: Contribution to journal › Article › peer-review

93 Scopus citations

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.

Original language	English
Pages (from-to)	100-104
Number of pages	5
Journal	Science
Volume	367
Issue number	6473
DOIs	https://doi.org/10.1126/science.aaz4352
State	Published - Jan 3 2020

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title = "TTC5 mediates autoregulation of tubulin via mRNA degradation",

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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T1 - TTC5 mediates autoregulation of tubulin via mRNA degradation

AU - Lin, Zhewang

AU - Gasic, Ivana

AU - Chandrasekaran, Viswanathan

AU - Peters, Niklas

AU - Shao, Sichen

AU - Mitchison, Timothy J.

AU - Hegde, Ramanujan S.

PY - 2020/1/3

Y1 - 2020/1/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85077476517

U2 - 10.1126/science.aaz4352

DO - 10.1126/science.aaz4352

M3 - Article

C2 - 31727855

SN - 0036-8075

VL - 367

SP - 100

EP - 104

JO - Science

JF - Science

IS - 6473

ER -

TTC5 mediates autoregulation of tubulin via mRNA degradation

Abstract

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