skip to main content
Idioma:

Paip2A inhibits translation by competitively binding to the RNA recognition motifs of PABPC1 and promoting its dissociation from the poly(A) tail

Sagae, Takeru ; Yokogawa, Mariko ; Sawazaki, Ryoichi ; Ishii, Yuichiro ; Hosoda, Nao ; Hoshino, Shin-ichi ; Imai, Shunsuke ; Shimada, Ichio ; Osawa, Masanori

The Journal of biological chemistry, 2022-05, Vol.298 (5), p.101844-101844, Article 101844 [Periódico revisado por pares]

United States: Elsevier Inc

Texto completo disponível

Citações Citado por
  • Título:
    Paip2A inhibits translation by competitively binding to the RNA recognition motifs of PABPC1 and promoting its dissociation from the poly(A) tail
  • Autor: Sagae, Takeru ; Yokogawa, Mariko ; Sawazaki, Ryoichi ; Ishii, Yuichiro ; Hosoda, Nao ; Hoshino, Shin-ichi ; Imai, Shunsuke ; Shimada, Ichio ; Osawa, Masanori
  • Assuntos: isothermal titration calorimetry ; NMR ; PABP-interacting protein 2A ; poly(A)-binding protein C1 ; RNA recognition motif ; surface plasmon resonance
  • É parte de: The Journal of biological chemistry, 2022-05, Vol.298 (5), p.101844-101844, Article 101844
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Eukaryotic mRNAs possess a poly(A) tail at their 3′-end, to which poly(A)-binding protein C1 (PABPC1) binds and recruits other proteins that regulate translation. Enhanced poly(A)-dependent translation, which is also PABPC1 dependent, promotes cellular and viral proliferation. PABP-interacting protein 2A (Paip2A) effectively represses poly(A)-dependent translation by causing the dissociation of PABPC1 from the poly(A) tail; however, the underlying mechanism remains unknown. This study was conducted to investigate the functional mechanisms of Paip2A action by characterizing the PABPC1–poly(A) and PABPC1–Paip2A interactions. Isothermal titration calorimetry and NMR analyses indicated that both interactions predominantly occurred at the RNA recognition motif (RRM)2–RRM3 regions of PABPC1, which have comparable affinities for poly(A) and Paip2A (dissociation constant, Kd = 1 nM). However, the Kd values of isolated RRM2 were 200 and 4 μM in their interactions with poly(A) and Paip2A, respectively; Kd values of 5 and 1 μM were observed for the interactions of isolated RRM3 with poly(A) and Paip2A, respectively. NMR analyses also revealed that Paip2A can bind to the poly(A)-binding interfaces of the RRM2 and RRM3 regions of PABPC1. Based on these results, we propose the following functional mechanism for Paip2A: Paip2A initially binds to the RRM2 region of poly(A)-bound PABPC1, and RRM2-anchored Paip2A effectively displaces the RRM3 region from poly(A), resulting in dissociation of the whole PABPC1 molecule. Together, our findings provide insight into the translation repression effect of Paip2A and may aid in the development of novel anticancer and/or antiviral drugs.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
Links
Voltar para lista de resultados
Ir para página anteriorAnterior Resultado  2 AvançarIr para próxima página

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.