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40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling

Author

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  • David J. Young

    (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health)

  • Sezen Meydan

    (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
    National Institute of General Medical Sciences, National Institutes of Health)

  • Nicholas R. Guydosh

    (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health)

Abstract

The recycling of ribosomes at stop codons for use in further rounds of translation is critical for efficient protein synthesis. Removal of the 60S subunit is catalyzed by the ATPase Rli1 (ABCE1) while removal of the 40S is thought to require Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR). However, it remains unclear how these Tma proteins cause 40S removal and control reinitiation of downstream translation. Here we used a 40S ribosome footprinting strategy to directly observe intermediate steps of ribosome recycling in cells. Deletion of the genes encoding these Tma proteins resulted in broad accumulation of unrecycled 40S subunits at stop codons, directly establishing their role in 40S recycling. Furthermore, the Tma20/Tma22 heterodimer was responsible for a majority of 40S recycling events while Tma64 played a minor role. Introduction of an autism-associated mutation into TMA22 resulted in a loss of 40S recycling activity, linking ribosome recycling and neurological disease.

Suggested Citation

  • David J. Young & Sezen Meydan & Nicholas R. Guydosh, 2021. "40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23223-8
    DOI: 10.1038/s41467-021-23223-8
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    Cited by:

    1. Yu H. Sun & Ruoqiao Huiyi Wang & Khai Du & Jiang Zhu & Jihong Zheng & Li Huitong Xie & Amanda A. Pereira & Chao Zhang & Emiliano P. Ricci & Xin Zhiguo Li, 2021. "Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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