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Updated: Aug 24, 2025

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mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading

Koichi Ogami1, Yuka Oishi1, Kentaro Sakamoto1

  • 1Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.

Cell Reports
|October 26, 2022
PubMed

Insights

Translation of 5' terminal oligopyrimidine (TOP) mRNAs is regulated by poly(A) tail length. LARP1 protein controls TOP mRNA polyadenylation, selectively accumulating long-tailed mRNAs during amino acid starvation to resume protein synthesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Translation of 5' terminal oligopyrimidine (TOP) mRNAs, which encode protein synthesis machinery, is regulated by the amino-acid-sensing mTOR pathway.
  • The precise regulatory mechanism for TOP mRNA translation remains largely unknown.

Purpose of the Study:

  • To elucidate the regulatory mechanism of TOP mRNA translation in response to amino acid availability.
  • To investigate the role of poly(A) tail length and RNA-binding proteins in this process.

Main Methods:

  • Analysis of TOP mRNA translation and poly(A) tail length under varying amino acid conditions.
  • Investigation of the RNA-binding protein LARP1's function and interactions.
  • Assessment of LARP1's role in polyadenylation and TOP mRNA accumulation.

Main Results:

  • TOP mRNA translation positively correlates with poly(A) tail length under mTOR-active conditions.
  • Poly(A) tail length of TOP mRNAs dynamically changes with amino acid availability, shortening when mTOR is active and lengthening during starvation.
  • The RNA-binding protein LARP1 interacts with poly(A) polymerases to regulate poly(A) tail length and is crucial for selective TOP mRNA accumulation during amino acid starvation.

Conclusions:

  • TOP mRNA translation is post-transcriptionally controlled by poly(A) tail-length regulation.
  • LARP1 mediates the selective accumulation of long-tailed TOP mRNAs under amino acid starvation.
  • This LARP1-dependent mechanism ensures rapid resumption of protein synthesis upon nutrient refeeding.
Keywords:
CP: Molecular biologyLARP1TOP mRNAamino acid starvationdeadenylationmTORpoly(A) tailpolyadenylationribosometranslation

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